ivane javaxisvilis saxelobis tbilisis saxelmwifo...
TRANSCRIPT
1
ivane javaxiSvilis saxelobis Tbilisis saxelmwifo universiteti,
medicinis fakulteti
iv. javaxiSvilis sax. Tsu al. naTiSvilis sax. morfologiis instituti.
klinikuri da eqsperimentuli paTologiis departamenti
xelnaweris uflebiT
irakli lacabiZe
aloqsanuri diabetis dros preparati plaferonis da sinTezuri
radioinertuli androgen meTiltrienolonis zemoqmedebis pirobebSi
pankreasSi mimdinare kompesaciur-adaptaciuri procesebi
disertacia
warmodgenili medicinis doqtoris akademiuri xarisxis mosapoveblad
samecniero xelmZRvaneli:
med.Mmec. doqtori akad.
med.Mmec. doqtori prof. Teimuraz jorbenaZe
konsultantebi:
med. mec. doqtori. T. RvamiCava
med. doqtori. n. didebuliZe
Tbilisi 2015
Nnino javaxiSvili
avtoris stili daculia
2
სარჩევი
შესავალი ........................................................................................................................................ 4
პრაქტიკული ფასეულობა ........................................................................................................ 11
ლიტერატურის მიმოხილვა ..................................................................................................... 12
მასალა და მეთოდები .............................................................................................................. 25
ალოქსანი ................................................................................................................................. 26
პლაფერონი LB ........................................................................................................................ 26
ჰისტოლოგიური კვლევა ....................................................................................................... 26
ელექტრონულ-მიკროსკოპული კვლევა ............................................................................. 27
იმუნოჰისტოქიმიური კვლევა .............................................................................................. 28
ელექტრონul-რადიოავტოგრაფული და რადიოიმუნური კვლევა ............................. 28
სტატისტიკური ანალიზი...................................................................................................... 29
გამოკვლევის შედეგები ............................................................................................................ 30
ვირთაგვების პანკრეასის მორფო-ფუნქციური თავისებურებანი ალოქსანური
დიაბეტის დროს ..................................................................................................................... 30
დანართი 1 ................................................................................................................................... 40
მორფოლოგიური ცვლილებები ვირთაგვების პანკრეასში ალოქსანური დიაბეტის
დროს და პლაფერონის ზემოქმედების შემდეგ ................................................................... 56
დანართი 2 ................................................................................................................................... 60
ალოქსან-პლაფერონის ჯგუფის ვირთაგვების პანკრეასში კუნძულ გარეთ არსებული
იზოლირებული β-უჯრედები და მათი ფუნქციური მდგომარეობის შეფასება
ელექტრონულ-მორფომეტრული მეთოდით ....................................................................... 74
დანართი 3 ................................................................................................................................... 76
ჰორმონალურ-მეტაბოლური ცვლილებები მამრ ვირთაგვებში ალოქსანური
დიაბეტის დროს და სინთეზური რადიოინერტული ანდროგენ მეთილტრიენოლონoს
ზემოქმედების შემდეგ .............................................................................................................. 78
დანართი 4 ................................................................................................................................... 79
გამოკვლევის შედეგების ანალიზი ......................................................................................... 81
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დასკვნა ....................................................................................................................................... 100
SUMMURY ................................................................................................................................. 104
გამოქვეყნებული შრომების სია ............................................................................................ 107
ლიტერატურა ........................................................................................................................... 108
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შესავალი
sadReisod, jandacvis aqtualur sakiTxs warmoadgens Saqriani
diabeti, romelic ara marto samedicino problemaa, aramed aqvs didi
socialur-ekonomikuri mniSvneloba, gavrcelebis sixSiris, invalidobis
da sicocxlis xangrZliobis TvalTaxedviT, ara marto saqarTveloSi,
aramed msoflioSi.
mravalricxovani kvlevebi (1-4) eZRvneba am avadmyofobis
epidemiologias, klinikas, morfologias da sikvdilis mizezebs. bolo
wlebis miRwevebma Saqriani diabetis daavadebulTa diagnostikaSi, farTo
dispanserizaciam, axali preparatebis Seqmnam da gamoyenebam
(prolongirebuli insulini da sxva Saqardamwevi saSualebebi), Zireulad
Secvala am avadmyofobis klinikuri mimdinareoba da gazarda sicocxlis
xangrZlioba, Tumca samwuxarod mainc ar SeimCneva am avadmyofobis
klebis tendencia. sxvadasxva qveynebSi Catarebuli kvlevebis safuZvelze
dadgenilia, rom msoflioSi mosaxleobis 2% daavadebulia Saqriani
diabetiT da yovel erT gamovlenil SemTxvevaze modis am avadmyofobis
erTi gamouvleneli forma. e.i. gaaCniaT farulad mimdinare Saqriani
diabeti. mosaxleobis 3% ki aqvs genetikurad ganpirobebuli Saqriani
diabeti. cnobilia, rom mTeli endokrinuli daavadebebis struqturaSi
50% modis Saqrian diabetze (5).
Tanamedrove paTomorfologiis erT-erT mniSvlovan sakiTxs
waრmoadgens qsovilTaSorisi urTierToba. kerZod, parenqima-
mikrocirkulaciuri sistema-SemaerTebeli qsovili - es is kvanZia,
romlis erTiani gaTvaliswinebis gareSe SeuZlebelia viqonioT sruli
warmodgena organizmSi mimdinare paTologiur da adaptaciur
procesebsze.
eqsperimentuli, klinikuri, morfologiuri gamokvlevebis safuZvelze
dadgenilia Saqriani diabetis ganviTarebis paTogenetikuri koncefcia da
gamoyofilia am avadmyofobis ramodenime qvetipi, magram aSkaraa, rom
ZiriTadi mizezi, romelic ganapirobebs daavadebis manifestaciis vadas,
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daavadebis simZimes pankreasis kunZulebis β-ujredebis dazianebis
xarisxia. swored es gansazRvravs am ujredebis morfologiuri
mdgomareobis Seswavlis interess.
Saqriani diabeti metaboluri da imunuri procesebis moSlis
generalizebuli avadmyofobaa. bolo wlebSi mecnierebis interess
iwvevs Saqriani diabetis zegavlena SemaerTebeli qsovilis
metabolizmze, romelic garda rigi sxva mniSvnelovani funqciebisa
garkveul rols TamaSobs sisxlZarRvis kedlis dazianebis paTogenezSi.
cnobilia, rom pankreasis kunZulebis mikrovaskulაrizaciis ganviTareba
ganpirobebulia urTierTobebiT kunZulebis β-ujredebsa da endoTelur
ujredebs Soris. swored am ujredebis urTierTkavSiriT xdeba
pankreasis kunZulebis mier sekretoruli funqciis uzrunvelyofa.
bolo wlebis monacemebi pankreasis kunZulebis mikrocirkulaciur wreSi
mimdinare cvlilebebze sakmaod qaoturi da winaaRmdegobrivia da aseve
warmoadgens kvlevis mniSvnelovan sagans.
β-ujredebi uSualo kontaqtSi imyofebian pankreasis Aα da δD
ujredebTan, romlebic Tavis mxriv aproducireben glukagons da
somatostatins. Saqriani diabetis sxvadasxva simZimis dros am samive
saxis ujredebis urTierTdamikidebuleba sakmaod rTulia da iTxovs
Semdgom Seswavlas.
Saqriani diabetis dros β-ujredebis proliferacia mniSvnelovnad
CamorCeba maT aRwarmoebas. zemoTqmulidan gamomdinareMmniSvnelovan
Teoriul da praqtikul interess warmoadgens regeneraciuli, aRdgeniTi
procesebis Seswavla pankreasSi am paTologiis pirobebSi. problemis
irgvliv arsebuli informaciis retrospeqtruli analizi (6-9) gviCvenebs,
rom sadReisod gamoikveTa ramodenime aqtualuri sakiTxi. kerZod,
kompensaciur-adaptaciuri procesebis Seswavlisas gansakuTrebuli
yuradReba eniWeba kunZulgareT da kunZulebSi arsebul gardamavali
tipis ujredebs specialuri insulinisaTvis damaxasiaTebeli granulebiT
da Rerovan ujredebs. pasuxis gacemas iTxovs mTeli rigi sakiTxebisa:
saidan warmoiSva es insulinis granulebis Semcveli ujredebi, ra aris
am ujredebis winamorbedebi, rogor xvdeba insulini am ujredebidan
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sisxlSi, SeiZleba Tu ara, CaiTvalos es ujredebi kompensatorul
gamovlinebad hormonis ukmarisobaze da aris Tu ara am gardamavali
tipis ujredebis gaaqtiurebis SesaZlebloba.
Saqriani diabetis dros gansakuTrebuli yuradReba eTmoba
reproduqciuli hormonebis, kerZod androgenebis monawileobas
pankreasis kunZulebSi mimdinare adaptaciur procesebSi. cvlilebebi
androgenebis metabolizmSi gavlenas axdenen anabolizmis procesebze,
romlebic Tavis mxriv regulirdeba insuliniT da Sesabamisad amZimeben
Saqriani diabetis mimdinareobas. Lliteraturuli monacemebiT (10)
androgen receptorebi monawileobas Rebuloben ujredebSi mimdinare
iseT rTul procesebSi, rogoricaa proliferacia, diferenciacia,
apoptozi. zemoTqmulidan gamomdinare gasagebi xdeba interesi
androgenebis rolisadmi β-ujredebis adaptaciaSi Saqriani diabetis
dros.
Saqriani diabeti qronikulad mimdinare avadmyofobaa, Sesabamisad
pacientebze SeuZlebelia yvela im gamokvlevebis Catareba, romlebic
zustad asaxavs im morfologiur cvlilebebs, romlebic viTardeba
pankreasSi sxvadasxva simZimis Saqriani diabetis dros.
zemoTqmulidan gamomdinare kvlevis mizania aloqsanuri diabetis
eqsperimentul modelze Wistar-is jiSis virTagvebze:
1. Segveswavla უnatifesi morfologiuri cvlilebebi (ujredul da
subujredul doneze), romelic viTardeba pankreasis kunZulebSi
eqsperimentuli diabetiს sxvadasxva simZimis paTologiuri procesis
dros.
2. gamogvevlina is morfologiuri cvlilebebi, romlebic saSualebas
mogvcems ganvsazRvroT dazianebis xarisxi da moculoba raTa Segveqmnas
sruli warmodgena paTologiuri da adaptaciuri procesis
mimdinareobaze aloqsanuri diabetis dros.
3. gangvesazRvra pankreasSi mimdinare regeneraciuli procesebi
aloqsanuri diabetis dros, plaferoniT (amnioturi peptidi) da
sinTezuri radioinertuli androgen- meTiltrienoლონის zemoqmedebis
Semdeg.
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miRebul monacemebze dayrdnobiT SesaZlebeli iqneba gamovavlinoT
is morfologiuri cvlilebebi, romelic viTardeba pankreasis
kunZulebSi da kunZul gareT aloqsanuri diabetis dros, plaferoniT da
sinTezuri radioinertuli androgen-meTiltrienolონis zemoqmedebis
Semdeg, rac udavod mniSvnelovani iqneba mkurnalobis saTanado da
optimaluri meTodebis SemuSavebisas.
8
კვლევის სიახლე
kvlevis kompleqsuri (histologiuri, იმუნოhistoqimiuri,
bioqimiuri, eleqtronuli, eleqtrono-radioavtografiuli, eleqrono-
morfometriuli da statistikuri) meTodebis gamoyenebiT
Seswavlilia pankreasis kunZulebi, mikrocirkulaციუri sistema,
SemaerTebeli qsovili, aloqsanuri diabetis sxvadasxva simZimis
paTologiuri procesis dros, plaferoniT (amnioturi peptidi) da
sinTezuri radioinertuli androgen-meTiltrienolონis zemoqmedebis
Semdeg.
aRwerilia pankreasis β-ujredebis morfo-funqciuri suraTi
aloqsanuri diabetis ganviTarebis da Camoyalibebis procesSi.
dadgenilia rom es cvlilebebi aris Saqriani diabetis klinikuri
gamovlinebis ZiriTadi morfologiuri maCvenebeli da asaxavs
aloqsanuri diabetis rogorc simZimes, ise stadias. es morfologiuri
maCvenebeli damokidebulia glukozis Semcvelobaze sisxlSi.
gamovlenilia urTierTdamokidebuleba erTis mxriv insulinis
warmomqmnel β-ujredebs da meores mxriv glukagonis da somatostatinis
warmomqmnel Aα da δD ujredebs Soris. dadgenilia, rom aloqsanuri
diabetis dros, pankreasis endokrinuli nawili kompleqsurad pasuxobs
naxSirwylebis cvlis moSlaze mTeli misi komponentebis met-naklebi
monawileobiT.
Ddadgenilia, rom aloqsanuri diabetis dros, pankreasis kunZulebis
mikrocirkulaციურ კალაპოტში ganviTarebul alteraciul cvlilebebs
(endoTelis distrofia, deskvamacia, nekrozi), mosdevs anTebiTi da
imunuri ujredebis migracia transendoTelur perikapilarul sivrceSi
da qsovilebSi, β ujredebis Semdgomi dazianebiT. miRebul monacemebze
dayrdnobiT SeiZleba vivaraudoT, rom β-ujredebis dazianebaSi erT-
erTi mTavari roli miekuTvneba cvlilebebs mikrocirkulaciur
კალაპოტში.Pplaferonis zemoqmedeba aZlierebs endoTelis
proliferacias da xels uwyobs angiogenezis procesis aqtivacias.
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morfologiuri gamokvlevebi mowmoben rom qsovilovan doneze
moqmedebs meqanizmiebi, romlebic avtomaturad uzrunvelyofen
parenqimisa da stromis urTierTregulacias. paTologiuri procesis
simZimიs proporciulad matulobs mwife fibroblastebis raodenoba,
kunZulebSi Cndeba uxeSi fibrozuli CanarTebi, irRveva pankreasis
kunZulebis struqtura. plaferoniT zemoqmedebis Semdeg aRiniSneba
SemaerTebeli qsovilis rezorbciis procesebis gaZliereba (aseT ubnebSi
Warbadaa makrofagebi). savaraudoa, rom plaferoniT zemoqmedebis Semdeg
aqtiurdeba makrofagebi, romlebic xels uwyoben kolagenuri boWkoebis
liziss.
aloqsanuri diabetis dros gamovlenilia kunZul gareT arsebuli
gardamavali tipis ujredebi β-ujredebis niSan TvisebebiT. dadgenilia,
gardamavali tipis ujredebi SedarebiT metia saSualo simZimis
aloqsanuri diabetis dros da mcirea mZimed mimdinare paTologiuri
procesis SemTxvevaSi, rac dadasturebaa imisa, rom es gardamavali
tipis ujredebi aris kompensatoruli procesis gamovlineba.
kvlevebiT dadgenilia, rom aloqsanuri diabetiT daavadebul
virTagvebis pankreasSi plaferoniT stimulaciis Semdeg gamovlenilia
Rerovani da gardamavali tipis ujredebი, zog ujredeბSi aRiniSneba
CD34, xolo zogSi CK19 mkveTri eqspresia. am ujredebs gaaCniaT maRali
sekretoruli aqtivoba da maTSi naklebad vlindeba destruqciuli
cvlilebebი. ეs ujredebi atareben, rogorc acinaruli, sadinrebis
epiTeluri, pankreasis kunZulSida endokrinuli da mezenqimuri, aseve Bβ-
ujredebis niSan Tvisebebs. miRebuli Sedegebis safuZvelze SeiZleba
vivaraudoT, rom gardamavali tipis ujredebs da Rerovan ujredebs
aqvT potencia neogenezis, diferenciaciis da transdiferenciaciis gziT
diferencirdnen pankreasis β-ujredebSi. amgvarad, rogorc Cans
pankreass stimulaciis Semdeg aqvs unari dasabami misces multipotentur
progenitorebs da Rerovan ujredebs.
kvlevis Sedegad mamr virTagvebSi aloqsanuri diabetis dros
aRiniSneba metaboluri da hormonaluri TviTregulaciis moSla,
romelic vlindeba, rogorc metaboluri stresi. xdeba adaptaciuri
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hormonebis mniSvnelovani zrda, aromatizaciis procesebis aqtivacia,
testosteronis raodenobis Semcireba, estradiolis raodenobis mateba,
dnm-isa da rnm-is sinTezis Semcireba. sinTezur radioinertuli
androgen-meTiltrienolონis Seyvanis Semdeg sisxlSi glukozis
koncentracia Semcirebulia, adaptaciuri hormonebis koncentracia
miaxloebulia normasTan, klebulobs aromatizaciis procesebis
aqtivacia. aRiniSneba dnm-isa da rnm-is sinTezis zrda, β-ujredebis
proliferaciis mateba. testosteronis miaxloeba normasTan, xels
uwyobs androgenuli receptorebis aqtivacias da organos mdgomareobis
gaumjobesebas.
miRebuli monacemebi saSualebas gvaZlevs viqonioT sruli
warmodgena im paTologiur da adaptaciur procesებze, romlებic
viTardeba pankreasis kunZulebSi, mis parenqimasa da stromaSi
aloqsanuri diabetis sxvadasxva simZimis paTologiuri procesis dros,
preparat plaferoniT da sinTezur radioinertuli androgen-
meTiltrienolონis zemoqmedebis Semdeg.
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პრაქტიკული ფასეულობა
miRebuli Sedegebi saSualebas gvaZlevs vimsjeloT im cvlilebze,
romlebic viTardeba pankreasSi eqsperimentuli diabetis pirobebSi,
plaferoniT da sinTezuri radioinertuli androgen-meTiltrienolonis
zemoqmedebis Semdeg. miRebuli monacemebi saSualebas gvaZlevs
vivaraudoT analogiuri cvlilebebis ganviTarebaze pacientebis
pankreasSi Saqriani diabetis dros, rogorc am daavadebis aucilebel
komponentze.
aRniSnul monacemebze dayrdnobiT SeiZleba gavakeToT rekomendacia
Saqriani diabetis sxvadasxva simZimis paTologiuri procesis dros
profilaqtikur, Tu samkurnalo RonisZiebebis mizanSewonilobaze da
SevimuSaoT mkurnalobis adeqvaturi meTodebi pankreasis endokrinuli
nawilis potenciuri SesaZleblobis gaTvaliswinebiT.
12
ლიტერატურის მიმოხილვა
E
β-ujredebi yvelaze mravalricxvovania pankreasis kunZulebis
ujredebs Soris, ganlagebulni arian kunZulis centrSi sisxlZarRvebis
garSemo da sxva endokrinul ujredebTan SedarebiT sisxlmomaragebis
TvalsazrisiT priviligirebul mdgomareobaSi imyofebian. β-ujredebis
funqciis daqveiTeba, iseve rogorc maTi raodenobis Semcireba, iwvevs
maT mier gamomuSavebuli hormonis deficits da erT-erT yvelaze
gavrcelebul mZime daavadebas Saqrian diabets (11-14).
histologiuri, eleqtronul-mikroskopuli, morfometruli kvlevebis
safuZvelze eqsperimentuli aloqsanuri diabetis dros Tagvebsa da
virTagvebSi mTeli rigi avtorebის (4, 15-20) mier naCvenebia pankreasis
kunZulebis hipertrofia, maTSi fibrozuli qsovilis kerebis warmoqmniT,
β-ujredebis ricxvis da simkvrivis Semcireba. β-ujredebis
ultrastruqturis Rrma dazianeba, gansakuTrebiT mkveTrad gamoxatuli
cvlilebi maT organelebsa da sekretorul granulebSi. zogierTi β-
ujredebis degranulacia, vakuolizacia, nekrozi. pankreasis kunZulebis
Cveulebrivi struqturis rRvevა.
qronikuli eqsperimentuli aloqsanuri diabetis dros zogi avtorebi
(21, 22) aRniSnaven pankreasis kunZulebis Semcirebas rogorc zomebSi ise
raodenobrivad, wilakTaSoris da acinusebs Soris fibrozs, sustad
gamoxatul limfocitarul infiltracias. atrofirebul kunZulebSi
ujredebis meti nawili Seicavs granulebis mcire raodenobas.
imunohistoqimiuri kvleviT atrofirebul kunZulebSi ujredebi ar
iZlevian reaqcias antiinsulinis da antisomatosatatinis antisxeulebze.
zogierTi nekrozuli kunZuli ganicdis kalcifikacias.
miuxedavad imisa, rom Saqriani diabetis ganviTarebaSi aSkaraa
insulinmaproducirebeli β-ujredebis roli, rigi mkvlevarebis (23-26)
azriT yuradReba unda mieqces agreTve αA da δD ujredebsac, romlebic
13
Sesabamisad gamohyofen hormonebs glukagons da somatostatins. rogorc
Cans am ujredebis reaqcia Saqriani diabetis dros araerTgvarovania,
damokidebulia avadmyofobis stadiaze, paTologiuri procesis simZimeze
da insulinis ukmarisobis xarisxze (27, 28).
H კvlevis histologiuri, imunohistoqimiuri da morfometriuli
meTodebis gamoyenebam eqsperimentuli aloqsanuri diabetis dros
virTagvebSi, SesaZlebeli gaxada avtorebs (23, 25, 28, 29) gamoevlinaT
pankreasis kunZulebSi β, Aα da δD ujredebs Soris arsebuli
urTierTdamokidebulebis aspeqtebi.
avtorebis (24, 30) mier Catarebuli imunohistoqimiuri da
morfometriuli kvlevis safuZvelze TagvebSi, romlebsac hqondaT
aloqsanuri diabeti dadginda pankreasis kunZulebSi β-ujredebis
odenobiTi simkvrivis Semcireba, maSin rodesac Aα da δD ujredebis
odenobiTi simkvrive momatebuli iyo.
Goke-s (27) gamokvlevებიT msubuqაd mimdinare eqsperimentuli
diabetis dros Aα da δD ujredebSi raime cvlilebebi ar aRiniSneba,
maSin rodesac diabetis mZime formis SemTxvevebSi β-ujredebi
ganicdian vakuolizacias, degranulacias, xoloAα da δD ujredebis
adgilmdebareoba Secvlilia periferiidan centrisaken.
Leiter et al. (26) ultrastruqturuli da imunohistoqimiuri kvlevis
safuZvelze, aloqsanuri diabetis dros TagvebSi eqsperimentis adreul
vadebze miuTiTeben β-ujredebis hipersekraciaze. maTi monacemebiTAα
daDδ ujredebi gadanacvlebulia kunZulis periferiidan centrisaken.
grZeli δD ujredebi penetrirebulia kunZulis siRrmeSi. mniSvnelovnad
gazrdilia Sexebis zedapiri Aα da δD ujredebs Soris. avtorebis (31)
mier eqsperimentSi radioimunuri da imunuhistoqimiuri kvlevis
meTodebis gamoyenebiT dadgenilia somatostatinis da glukagonis
raodenobis momateba sisxlSi, xolo insulinis koncentraciis Semcireba.
gazrdilia Aα da δ ujredebis raodenobac da zomebi, xolo β-ujredebis
Semcirebulia.
14
Tanamedrove morfologiis erT-erT centralur sakiTxs wamoadgens
qsovilTaSorisi urTierToba, kerZod parenqima-mikrocirkulaciuri
sistema-SemaerTebeli qsovili.
pankreasi aris maRali donis vaskuolirizaciis mqone organo,
romelsac aqvs SesaZlebloba awarmoos insulinis sekreti da
areguliros glukozis done sisxlSi (32, 33). gamokvlevebis safuZvelze
dadgenilia, rom Saqriani diabetis dros sxvadasxva organoebis wvril
sisxZarRvebSi, kerZod mikrocirkulaciur sistemaSi aRiniSneba
sisxlZarRvis kedlis hialinozi, plazmuri gaJRenTva, kedlis gasqeleba,
intimis gafaSreba da adgil-adgil endoTelis proliferacia.
morfologiuri cvlilebebis kompleqsi viTardeba mikrocirkulaciuri
sistemis, rogorc sisxlZarRvebSi, aseve perivaskularul zonaSi.
Aavtorebis (34-37) azriT pankreasis kunZulebi es is modelia,
romelzedac kargad Seiswavleba mikrovaskularuli kalapoti β-
ujredebTan erTad. rigiAmkvlevarebis (38, 39) mier aRwerilia pankreasis
kunZulebis kapilarebis morfologia da maTi roli kunZulebis
fiziologiuri funqciis ganviTarebaSi. Nnawilobriv Seswavlilia
pankreasis kunZulebis mikrocirkulaciis roli 1 tipis diabetis dros.
gamovlenilia pankreasis kunZulebSi sekretirebuli WEGF-A-s
(vaskulარuლ-endoTeluri zrdis faqtoris) moqmedeba endoTelis
gamtarobaze, ganxilulia mikrovaskularuli qselis ganviTareba da
funqcia janmrTel da daavadebul qsovilebSi. rigi avtorebis (33, 40)
monacemebiT insulindeficitur Tagvebis pankreasis kunZulebSi meti
kapilarebia, vidre janmrTeli Tagvebis pankreasis kunZulebSi,
Sesabamisad, kunZulebic ufro didia.
gansxvavebuli eqsperimentebis safuZvelze warmoiqmna azri (38, 40),
rom endoTeluri ujredebi ganapirobeben kunZulebis ganviTarebas.
bolo wlebis monacemebi pankreasis kunZulebis mikrocirkulaciur
სისტემაში mimdinare cvlilebebis paTo da morfogenezze Saqriani
diabetis dros sakmaod winaaRmdegobrivia. paTologebisaTvis da
klinicistebisaTvis sakmaod mniSvnelovania am cvlilebebis
morfogenezis kompleqsuri analizi. zemoTqmulidan gamomdinare, naTelia
Tu ra mniSvneloba aqvs im cvlilebebis Seswavlas, romlebic viTardeba
15
pankreasis kunZulebis mikrocirkulaciur სისტემაში Saqriani diabetis
dros.
Ptak-is (41) mier sinaTlis da eleqtronuli mikroskopiT Seswavlilia
Tagvebis pankreasis kunZulebi eqsperimentuli aloqsanuri diabetis
dros. maTi monacemebiT eqsperimentis sawyis vadebze aRiniSneba Zlieri
mononuklearuli infiltracia, rogorc pankreasis kunZulebSi, aseve
kunZulebis axlos. Espinoza et.al. (42) stresiT gamowveuli Saqriani diabetis
sawyis vadebze virTagvebis pankreasis kunZulebSi miuTiTeben
makrofagebis Zlier infiltraciaze. imunocitebi, romlebic avtorebis
mier identificirebuli iyo, rogorc makrofagebi imyofeboda
fagocitozis stadiaSi da inelebda daSlil β-ujredebs.
Vetere et al. (43) azriT Saqriani diabetis progresirebasTan erTad
makrofagebis raodenoba mcirdeba.
sakmaod sainteresoa imunokompetenturi ujredebis roli Saqriani
diabetis dros. cnobilia, rom I an iuveniluri tipis diabetis
SemTxvevaSi Timusidan miRebuli T-limfocitebi angreven kunZulebis β-
ujredebs.
NODDTagvebi (ara simsuqniT gamowveuli diabeti) xSirad gamoiyeneba
modelebad diabetis autoimunuri, anTebiTi formebis Sesaswavlad. Xu et
al. (44) aRniSnaven, rom I tipis diabetis dros endoTeluri ujredebis Sre,
romelic normalur pirobebSi warmoadgens bariers leikocitebisaTvis,
dazianebulia da saSualebas aZlevs T-limfocitebs Sevidnen kunZulebSi
da daazianon β-ujredebi.
amgvarad arsebuli literaturuli monacemebi morfologiur
cvlilebebze pankreasSi eqsperimentuli diabetis dros arc ise cotaa,
Tumca MmiRebuli Sedegebi sakmaod gansxvavebulia, rac rogorc Cans
ganpirobebulia eqsperimentis sxvadasxva vadebiT, romelic tardeba
gansxvavebul eqsperimentul cxovelebze. zemoTqmulidan gamomdinare
aSkaraa Tu ra mniSvneloba aqvs yvela am cvlilebebis Seswavlas da
sistematizacias.
Saqriani diabetis dros did Teoriul da praqtikul interess
warmoadgens kunZulovan qsovilSi mimdinare kompensatoruli da
16
regeneraciuli procesebis Seswavla, ramdenadac am procesebis
intensioba ganapirobebs insularuli ukmarisobis simZimes. struqturul
doneze insularuli ukmarisobis kompensacia xorcieldeba ZiriTadad 2
gziT: hormonoproduqciis gaZlierebiT darCenili ujredebis funqciuri
aqtivobis gazrdis xarjze, an insularuli ujredebis raodenobis
momatebiT (45-48).
β-ujredebis Senacvlebis Terapiis gamoyenebis სaWiroebam, rac
warmoadgens β-ujredebis transplantaciis (49) alternativas , gamoiwvia
kvleviTi samuSaoebis Catarebis აუცილებლობა β-ujredebis generaciis
sakiTxebze pankreasis (50-54) da ara pankreasis warmoSobis gansxvavebuli
ujredebidan (54-57).
kvlevebisa da axali hipoTezebis safuZvelze aRwerilia β-
ujredebis aRdgenis gansxvavebuli gzebi: arsebuli β-ujredebis
replikaciiT (50, 52, 58) da proliferaciiT (59-67), pankreasis sadinrebis
epiTelis neogeneziT da diferenciaciiT (68-79) pankreasis
diferencirebuli ujredebis (acinaruli, pankreasis sadinrebis
epiTeluri) transdiferenciaciiT (80-85), pankreasis zogierTi kunZulSida
arsebuli ujredebis neogeneziT da transdiferenciaciiT (86-89),
pankreasis gareT arsebuli ujredebis da Rerovani ujredebis
diferenciaciiT e.w. transdiferenciaciiT (6, 55-57, 70, 90-99). D
Liu et al. (94) azriT eqsperimentul TagvebSi β-ujredebis generacia
winamorbedi ujredebidan damokidebulia kunZulebis dazianebis xarisxze
da cxovelebis asakze. Tschen et al. (100) monacemebiT asakovan TagvebSi Bβ-
ujredebis generaciis unari Semcirebulia. De Tata et al. (101) aseve Tvlian,
rom es procesi Senelebulad mimdinareobs asakovan TagvebSi.
Waguri M. et.al. (102) Seiswavles ra ujredebSi mimdinare regeneraciuli
procesebi, daadgines, rom aloqsanis perfuziiT gamowveuli seleqciuri
dazianebis dros pankreasis kunZulebis segmentებSi aRiniSneba β-
ujredebis destruqcia, xolo araperfuzirebul segmentebSi β-ujredebi
SenarCunebulia. histologiuri suraTis mixedviT aloqsaniT
perfuzirebul segmentebSi gamovlenilia axlad warmoqmnili kunZulebi,
maSin rodesac araperfuzirebul segmentebSi aRiniSneba arsebuli β-
17
ujredebis proliferacia. eqsperimentis adreul vadebze kunZulebi,
rogorc zomiT ise raodenobrivad Semcirebulia, maSin roca mogvianebiT
matulobs kunZulebis mimdinare sivrce, izrdeba calkeuli β-ujredebis
zoma, romlebic axlo SexebaSia sadinris epiTelTan da rogorc Cans am
ujredebidan diferencirdebian. avtorebis azriT axali β-ujredebis
diferenciacia da proliferacia aris pankreasis kunZulebis
regeneraciis gamoxatuleba.
rigi mklevarebis (60, 61, 65) azriT pankreasis endokrinul nawils
gaaCnia proliferaciis maRali unari. jer kidev Д. Ф. Благовидов, Д. С.
Саркисов (103) erTeul SemTxvevebSi aRniSnaven insularuli qsovilis
mkveTrad gamoxatul hiperplazias da, rom pankreasis rezeqciis Semdeg
darCenili qsovili ZiriTadad warmodgenilia kunZulovani ujredebiT.
pankreasis kunZulovani qsovilis mniSvnelovan momatebas pankreasis
rezeqciis Semdeg cxovelebSi adastureben Semdegi avtorebi (104-106). maTi
monacemebiT kunZulebis zrda xdeba darCenil kunZulebSi ujredebis
hiperplaziis, proliferaciis da replikaciis Sedegad an egzokrinuli
ujredebis endokrinul ujredebad formirebis gamo.
cnobilia, rom pankreasis kunZulebis β-ujredebs axasiaTebs
SezRuduli mitozuri aqtivoba. rigi avtorebis (107, 108) azriT dabali
mitozuri aqtivoba kritikuli xdeba insulindamokidebul diabetian
TagvebSi, romlebsac mkveTrad aqvT gamoxatuli β-ujredebis destruqcia.
saintereso kvlevebia (97, 109) Catarebuli embrionuli Rerovani
ujredebis insulinis Semcvel β-ujredebad diferenciaciis dasadgenad.
bolo wlebis dakvirvebebma (88, 98, 110) gviCvenes, rom Rerovani ujredebis
diferenciacia funqciurad aqtiur β-ujredebamde mimdinareobs sakmaod
nela, Aalternativaa organos Rerovani ujredebis identifikacia,
eqspansia, diferenciacia an arsebuli β-ujredebis replikaciaBBBonner-Weir
et al. (83). winamorbedebi, romlebic gamoyofili iyo embrionidan
warmoadgendnen namdvil Rerovan ujredebs, maSin rodesac winamorbedebi
gamoyofili zrdasruli pankreasidan in-vivo warmoadgendnen mouwifebul,
dediferencirebul ujredebs (93, 98, 111-113).
18
De Haro-Hernandes R.et al. (114) monacemebiT Fgama transgenur TagvebSi
kunZulebis β-ujredebis regeneracia ori gansxvavebuli gziT
xorcieldeba: sadinrebis epiTeliuri ujredebidan an arsebuli β-
ujredebis funqciuri aqtivobis gaZlierebiT.
Gu D. et.al. (63, 115, 116) Tvlian, rom streptozotociniani diabetis
dros transgenur TagvebSi xdeba pankreasis sadinrebTan axlos
arsebuli erTeuli ujredebis regeneracia da neogenezi. maTive
monacemebiT tranzituli ujredebi Seicaven rogorc egzokrinul, aseve
endokrinul granulebs, romlebic xSirad Cndebian streptozotocinis
maRali dozis Seyvanis Semdeg. Aamgvarad, avtorebi Tvlian, rom axali β-
ujredebi warmoiqmneba kunZulebSi pankreasis sadinrebis epiTeluri
ujredebidan.
dResdReobiT warmodgenilia β-ujredebis neogenezis gziT miRebis
Semdegi meqanizmebi: pankreasis sadinrebis epiTeluri ujredebis
dakvirtvis Sedegad miRebuli ujredebis diferenciacia da Semdgom
hormonis warmoqmna (58, 72-74) da sadinrebTan axlos myofi ujredebis
proliferacia. sakmaod Zneli Sesafasebelia am ori meqanizmidan romeli
TamaSobs ufro mniSvnelovan rols aRdgeniT procesebSi, Tumca ki,
avtorebis (58, 72) umetesoba emxroba pirvels. amgvarad β-ujredebis
neogenezi pankreasis sadinrebis epiTelis dakvirtviT da Semdgomi
diferenciaciiT SedarebiT kargad aris Seswavlili da dokumentirebuli
(58, 78).
Collombat P.H., et al. (117, 118) mier transkripciuli faqtoris Pax4-s
kontrolis qveS miRebuli difteriis toqsinis gamoyenebis Semdeg,
sadinris epiTeluri ujredebi warmoqmnian rogorc acinarul, aseve
endokrinul ujredebs. aqedan 60%-Si xdeba β-ujredebis aRdgena
hiperglikemiis cvlilebebiT. elastazas toqsinis gamoyenebis Semdeg ki
aRiniSneba acinaruli ujredebis kvdoma, am SemTxvevaSi pankreasis
sadinrebis epiTeluri ujredebi dasabams aZleven acinaruli ujredebs.
Brun et al.-is (119) kvleviT diabetian TagvebSi transkripciuli faqtoriP
Pax4 aaqtiurebs β-ujredebis proliferacias.
19
pankreasis kunZulebis realur zrdas mRrnelebSi da adamianebSi
winamorbedebisagan Tavis kvlevebSi aRniSnaven Bonner-Weir et al. (113, 120).
maTi monacemebiT mRrnelebSi da virTagvebSi sadinrebis epiTelidan β-
ujredebis miReba mimdinareobs or talRad. 1. dabadebisTanave da 2. ZuZus
danebebis Semdeg. arsebobsHhipoTeza, rom postnatalur პერიოდში
kunZulebis ganviTarebis mTavar gzaს warmoadgens neogenezi da rom
pankreasis sadinrovan epiTeliums aqvs unari warmoqmnas axali kunZulebi
(75, 121).
rigi avtorebis azriT (122, 123) neogenezis procesis
gaaqtiurebisaTvis aucilebelია winamorbedi ujredebis stimulacia
sxvadasxva agentebiT; magaliTad zrdis faqtoriT (124), zrdis
epidermuli faqtoriT (67, 125), gastriniT (126, 127), glukagonis msgavsi
peptidebiT (128-130), aqtiviniT da betaceluliniT (131, 132), eqsidin-4-iT
(133, 134) da sxva faqtorebiT. zemoTCamoTvlili nivTierebebi calcalke
an kombinaciaSi astimulireben neogenezs. neogenezis Sesaxeb monacemebi
sakmaod gansxvavebulia da rogorc Cans ganpirobebulia Saqriani
diabetis gansxvavebuli eqsperimentuli modelebidan miRebuli SedegebiT,
romelSic monawileoben sxvadasxva cxovelebi Tagvebi, virTagvebi,
bocverebi da sxva. arsebuli Sromebi (53, 86, 128, 135) miuTiTeben
neogenezis arsebobaze, rogorc axalSobilebSi, aseve zrdasrul
organizmis pankreasSi kunZulebis dazianebis dros. M rigi avtorebi (106,
136) aseve aRweren Tagvebisa da virTagvebis pankreasis qsovilSi
mimdinare regeneraciul procesebs, sxvadasxva dazianebis SemTxvevebSi
da stimulaciis Semdeg. savaraudoa, rom sadinrovani ujredebis
populaciebi muSaoben, rogorc multipotenturi winamorbedebi romlebic
axdenen, rogorc egzokrinuli, aseve endokrinuli ujredebis generacias
(113, 137-139).
dResdReobiT β-ujredebis neogenezi warmodgenilia sadinrebis
dakvirtuli epiTeluri ujredebidan da aseve replikaciiT (50, 52, 58),
magram arc erTi ar warmoadgens eqskluzivs. axali β-ujredebis miReba
winamorbedebisagan garda am ori meqanizmisa SeiZleba moxdes
transdiferenciaciis gziTac (82, 140-143).A BB
20
Bonner-Weir et al.-is (58) monacemebze dayrdnobiT wamoyenebulia
hipoTeza, rom pankreasis sadinrebis diferencirebul epiTelur
ujredebs SeuZliaT funqcionireba dabadebis Semdeg, rogorc axali
kunZulebis winamorbedebs, momavalSi xdeba am ujredebis replikacia da
regresi ufro naklebad diferencirebul fenotipebSi da mxolod amis
Semdeg SeiZleba moxdes axali kunZulebis da acinusebis formireba.
aSkaraa, rom transdiferenciaciis dros, regresi da dediferenciacia
adreul vadebze normaluri procesia (111, 144).
epiTeluri ujredebis dediferenciacia xSirad asocirdeba epiTelur
mezenqimur gardaqmnasTan (99, 145, 146). Carlsson et al.-s (147) miaCnia, rom
epiTelur mezenqimuri gardaqmna warmoadgens erT-erT fiziologiur
safexurs pankreasis qsovilebis regeneraciis procesSi.
mniSvnelovania diskusia, kerZod sakiTxi acinozuri da kunZulovani
ujredebis urTierTgardaqmnis SesaZleblobaze, romelic daiwyo jer
kidev didi xnis win da dRemde grZeldeba (148). adre arsebuli
warmodgenis Tanaxmad acinozur da kunZulis ujredebs gaaCniaT
erTimeoreSi gadasvlis unari Tumca Semdgomma monacemebma mTlianad ar
daadastura am azris siswore. acino-insularuli transformacia,
rogorc paTologiis dros, ise fiziologiur mdgomareobaSi aRwerilia
rig kvlevebSi (81, 85, 115). acinozuri ujredebis gardaqmna kunZulovanSi
xdeba acino-insularuli fazis doneze, romlis drosac arsebobs
garkveuli mdgomareoba acinussa da kunZulebis inkretorul ujredebs
Soris (α, β da δ). eleqtronul-mikroskopuli kvlevis safuZvelze
ავტორები (149). aRniSnaven, rom acino-insularuli transformacia iwyeba
acinozuri ujredebis bazalur nawilSi, icvleba mitoqondriebi,
mcirdeba granularuli endoplazmuri badis odenoba, izrdeba
ribosomebis ricxvi, Cndeba kunZulebis ujredebisaTvis damaxasiaTebeli
specifikuri granulebi, romelTa raodenoba TandaTanobiT matulobs.
rigi avtorebis mier (71, 85, 143, 150, 151) insulindamokidebuli
diabetiT daavadebulebSi histologiuri, imunohistoqimiuri meTodebiT
gamovlenilia β-ujredebis struqturuli Tvisebebis mqone ujredebi
pankreasis acinusebSi. acinarul β-ujredebs axasiaTebdaT maRali
21
sekretoruli aqtiვoba da amasTan ar aRiniSnebodaT aSkarad gamoxatuli
destruqciuli cvlilebebi, ramac safuZveli misca mkvlevarebs
ganexilaT es ujredebi, rogorc funqciurad aqtiuri ujredebi. nawili
mkvlevarebisa (81, 115) Tvlis, rom acinaruli ujredebi endokrinuli
ujredebis niSanTvisebebiT gardamavali tipis ujredebia, romlebic
warmoiqmneba acinარულi ujredebis endokrinulSi transformaciis
Sedegad.
Яглов-is (152) hormonaluri profilis mixedviT arCevs sami tipis
acino-kunZulovan ujredebs (α, β da δ) ganasxvavebs egzokrinul da
endokrinul tips. К. А. Зуфаров da Tanaavtorebma (149) Seiswavles ra
pankreasis kunZulovani aparati sxvadasxva funqciur mdgomareobaSi
daadgines, rom virTagvebs, romlebsac xangrZlivi drois ganmavlobaSi
periodulad aZlevdnen glukozas didi doziT, ganuviTardaT didi
raodenobiT acinaruli ujredebi β-ujredebis niSan TvisebebiT, xolo
virTagvebს, romlebic SimSilobდნen, moemataT acinaruli ujredebis
raodenoba Aβ-ujredebis niSanTvisebebiT. am monacemebma safuZveli misca
avtorebs evaraudaT acinozuri ujredebis endokrinul ujredebad
transformaciis SesaZleblobaze, Tumca am azrs ewinaaRmdegeba Яглов В. В.
(152), is am ujredebs miiCnevs damoukidebel ujredebad, romlebsac
gaaCniaT Tavisi damaxasiaTebeli funqcia. Catarebuli kvlevis
safuZvelze Tvlis, rom acino-insularuli ujredebi, ara garadamavali
tipis ujredebia, aramed damoukidebeli ujredebi, romlebic
warmoadgenen insulinmaproducirebeli qsovilis evoluciis magaliTs.
eqskretoruli da kunZulovani qsovilis urTierTkavSirze miuTiTebs Д.
Ф. Благовидов-i da Д. С. Саркисов-ic (103). sadinrovani ligaciis
SemTxvevebSi adamianebis da virTagvebis pankreasSi acino-insularul
transdiferenciaciaze miuTiTeben Tavis SromebSi rigi avtorebisa (81).
Tumca ki am avtorebma (153, 154) verc erT seriuli anaTalze ver
daafiqsires sadinrebis epiTeluri ujredebis gadasvla uSualod
kunZulovan ujredebSi sadinrovari ligacis dros.
22
Minami et al. (151) aRniSnaven, rom cxovelebSi (TagvebSi da
virTagvebSi) insulinis warmomqmneli ujredebis generacia xdeba
acinaruli ujredebidan transdiferenciaciis gziT.
acinaruli ujredebidan β-ujredis warmoqmnaze arsebuli Sromebi
sakmaod gansxvavebulia. mTeli rigi avtorebis SromebSi (111, 153, 155)
aRwerilia acinarul kunZulovani transdiferenciacia daDam procesis
stimulirebis gzebi.BTumca ki rigi kvlevebis (154) Tanaxmad
eqsperimentSi acinaruli ujredebidan warmoiqmneba acinaruli da
sadinrovani ujredebi da ara β-ujredebi. rigi mklevarebis (105, 136) mier
nawilobrivi pankreatomiis dros aRiniSneba axali acinaruli ujredebis
warmoqmna. cxadia sakiTxi acino-insularuli transformaciis Sesaxeb
jer kidev moiTxovs Seswavlas. sadReisod regeneratoruli procesis
gamoxatulebad SeiZleba miviCnioT is axal warmonaqmnebi, romlebic
viTardebian wvrili gamomtani sadinrebis epiTelidan.
β-ujredebis erT-erT potenciur wyarod miiCneva TviT kunZulebSi
arsebuli ujredebi. fakultaturi ujredebis proliferaciiT da
rediferenciaciiT xdeba β-ujredebis warmoqmna kunZulebSi (61, 104, 119).
glukagonis warmomqmneli ujredebi aris pirveli endokrinuli
ujredebi, romlebic ganicdian diferenciacias da transformacias
insulin warmomqmnel ujredebad replikaciis gziT (86, 87, 89).
eqsperimentul kvlevebSi aRwerilia β-ujredebis regeneracia
kunZulSida α-ujredebidan. TagvebSi, romlebSiac β-ujredebi
dazianebuli iyo streptozotociniT da glukagonis warmomqneli α-
ujredebi gvevlineboda rogorc β-ujredis fenotipi. eqsperimentis
dawyebidan ramodenime Tvis Semdeg avtori (29) aRniSnavs sisxlSi
glukozis donis normalizacias. igive Sedegebi iqna miRebuli TagvebSi,
romelTa β-ujredebi dazianebuli iyo streptozotociniT. α-ujredebis β-
ujredebSi gardaqmnis SesaZleblobaze streptozotocian TagvebSi aseve
miuTiTeben sxva avtorebic (118). sainteresoa Sromebi, romlebSiac
aRniSnulia rom eqtopiuri eqspresia Pax4 iwvevs α-ujredebis
transdiferenciacias β-ujredebSi (Tagvebi). arsebuli kvlevebi
aradamajerebelia da moiTxovs Semdgom gagrZelebas, raTa gavigoT
23
warmoadgenen, Tu ara α-ujredebi β-ujredebis warmoqmnisaTvis
potenciur wyaros.
damtkicebulia, rom ganviTarebis embrionalur periodSi pankreasis
kunZulebis egzokrinuli da endokrinuli nawili viTardeba erTi
embrionuli Canasaxidan-endodermidan. es ki imis sasrgeblod laparakobs,
rom mas SenarCunebuli aqvs morfologiuri poliponetoba (112, 121, 135,
137, 156).
mTeli rigi kvlevebisa (56, 95, 157, 158), aseve eZRvneba β-ujredebis
generacias arapankreasuli warmoSobis ujredebidan. mniSvnelovani cda
iyo migveRo β-ujredebi, RviZlidan, Zvlis tvinidan da amnioturi
siTxidan in vitro magram zemoT CamoTvlili mcdelobebi iyo an
aradamajerebeli an negatiuri.
Aamgvarad β-ujredebis intensiuri diferenciacia da regeneracia
xels uwyobs β-ujredebis masis zrdas da Sesabamisad hormon insulinis
kompensacias (45, 52, 159) arsebuli Sromebi miuTiTeben, rom axali β-
ujredebi SeiZleba Seivsos pankreasis sadinrovani, wilSigniTa
sadinrebTan axlos arsebuli, centroacinaruli, acinaruli, kunZulSida
endokrinuli da Rerovani ujredebidan. dRemde Catarebuli kvlevebi
winaaRmdegobrivia da srulad ar asaxavs ujredebSi mimdinare
kompensatoruli procesebis morfologiur suraTs. rogorc Cans, β-
ujredebSi mimdinare kompensatoruli procesebis morfologiuri
kriteriumi arasakmarisad aris Seswavlili da moiTxovs kvlevebis
Semdgom gagrZelebas. K
klinikuri da eqsperimentuli kvlevebiT (10, 160, 161) dadgenilia
reproduqciuli hormonebis roli pankreasSi mimdinare adaptaciur
procesebSi Saqriani diabetis dros. cnobilia, Saqriani diabetis erT-
erT seriozul garTulebas warmoadgens reproduqciuli asakis
mamakacebSi sasqeso funqciis rRveva ganpirobebuli androgenebis
metabolizmis moSliT. cvlilebebi androgenebis metabolizmSi, Tavis
mxriv gavlenas axdens anabolizmis procesebze, romlebic regulirdeba
insulinis mier. literaturuli monacemebiT (162) androgen receptorebi
aqtiur monawileobas Rebuloben pankreasis kunZulebis ujredebSi
24
mimdinare adaptaciur-kompensaciur procesebSi da androgenuli
regulaciis efeqturoba ganisazRvreba, rogorc hormonis koncentraciiT,
aseve androgenuli receptorebis SemcvelobiT organoSi.
rigi avtorebis (161, 162) azriT eqsperimentuli diabetis dros androgen
receptorebi Tagvebis pankreasis kunZulebSi aregulireben ujreduli
procesebis farTo speqtrs, iseTebs rogoricaa proliferacia,
diferenciacia, apoptozi. zemoTqmulidan gamomdinare naTeli xdeba Cveni
interesi egzogenuri anrogenebis moqmedebisadmi metabolur da
kompensatorul procesebze Saqriani diabetis dros. D
amgvarad aSkaraa Tu ra mniSvneloba aqvs pankreasSi mimdinare yvela
cvlilebebis Seswavlas da sistematizacias eqsperimentuli diabetis
pirobebSi.
25
მასალა და მეთოდები
eqsperimentSi gamoyenebuli iyo 8 kviris asakis Wistar-is jiSis, orive
sqesis 120 virTagva, daaxloebiT 200 gr woniT. aqedan 90 virTagva iyo
samizne, 30 ki sakontrolo. 90 samizne virTagva daiyo 3 jgufad. 1
jgufSi iyo 30 virTagva erT Tviani aloqsanuri diabetiT,Mmeore jgufSi
30 virTagva erT Tviani aloqsanuri diabetiT, romlebsac ukeTdebodaT
plaferonis (0,25 mg/g) ineqciebi kunTebSi 10 dRis ganmavlobaSi da
meoTxe jgufi-30 mamri virTagva aloqsanuri diabetiT, romlebsac ori
kviris ganmavlobaSi ukeTdeboda 0,5 mg sinTezuri radioinertuli
androgen-meTiltrienoloni intraperitonealurad. diabets viwvevdiT
aloqsanis 150 mg 10% iani xsnaris erTjeradi SeyvaniT
intraperitonealurad. sakontrolo da samizne cxovelebi
gadanawilebuli da moTavsebuli iyvnen galiebSi. oTaxSi 12/12 sT-iT
(dRe-Rame), naTel-bneli cikliT, 22-25 C temperaturaze. aloqsanis
Seyvanis Semdeg 24 saaTis ganmavlobaSi cxovelebi ikvebebodnen
Tavisuflad da iRebdnen Saqrian wyals. mTeli eqsperimentis
ganmavlobaSi virTagvebi imyofebodnen kvebis srulfasovan, Sereul
racionze da wyals iRebdnen SeuzRudavi raodenobiT. aloqsanuri
diabetis simZime isazRvreboda glukozisa da imunoreaqtiuli insulinis
(IRI) SemcvelobiT sisxlSi. cxovelebSi glukozis koncentracia
plazmaSi maRal dones aRwevda 2 dReSi, xolo stabiluri diabeti
yalibdeboda 2 kviris manZilze. masalas viRebdiT eqsperimentis
dawyebidan 30, 40 da 44 dRis Semdeg. Eeqsperimentis bolos xdeboda
cxovelebis dakvla. cxovelebis eqsperimentidan gamoyvana warmoebda
intraperitonealurad 1 % etaminal-natriumis SeyvaniT.
26
ალოქსანი
aloqsani (2, 4, 5, 6-pyrimidinetetrone) aris glukozis toqsiuri analogi,
romelic amorCeviTad moqmedebs insulinis mwaromebel β-ujredebze,
azianebs am ujredebs da iwvevs adamianebSi arsebuli I tipis msgavs
Saqrian diabets eqsperimentSi. (163, 164).
პლაფერონი LB
plaferoni miRebuli iyo placentis amnioturi garsidan 1980 wels.
Aal. naTiSvilis sax. Eeqsperimentuli morfologis institutSi
mecnierTa jgufis mir akad. v. baxutaSvilis xemZRvanelobiT. Seswavlili
iyo plaferonis qimiuri, biologiuri da Terapiuli Taviseburebebi (165,
166). Catarebuli gamokvlevebiT dadginda, rom plaferoni (amnioturi
peptidi) aris biologiurad aqtiuri nivTiereba, romelic xasiaTeba
anTebis sawinaaRmdego, imunomamodulirebeli, antivirusuli,
antibaqteriuli, antiapoptozuri, hipoglikemiuri TvisebebiT. D
ჰისტოლოგიური კვლევა
histologiuri gamokvlevisaTvis masala fiqsirdebოდა 10 %
formalinSi, karnuasa da buenis safiqsacio narevSi. 5, 10 da 30 mk.
parafinis anaTlebis SeRebვa xdeboda hematoqsilin-eoziniT,
aldegidfuqsiniT, grimeliusiT, tolouidinis lurjiT da
pikrofuqsiniT van-gizonis mixedviT.
27
ელექტრონულ-მიკროსკოპული კვლევა
eleqtronul-mikroskopuli kvlevisaTvis pankreasis qsovilis wvrili
nawilebi 2 saaTis ganmavlobაში Tavsdeboda koloidur buferze (Ph 7,2 -
7,4) axlad momzadebul 2% osmiumis mJavis xsnarSi +4 C,
Ggauwylovanebisa da aRmaval koncentraciis spirtebSi gatarebis Semdeg
masala yalibdebოდა aralditis an epon 812-is narevSi. polimerizacias
vawarmoebdiT +58 C ocdaoTxi saaTis ganmavlobaSi.
ultraTxeli anaTlebi mzaddeboda LKB-III ultratomze. masalas
vRebavdiT uranilacetatiT reinoldcis mixedviT. ris Semdeg tardebოდა
gamokvleva eleqtronuli mikroskopiT „TeslaBS-500“ (gadideba 9000 - 22000),
dabeWdvisas negatiuri gamosaxuleba diddeboda 3-5-ჯერ.
ელექტროnul-მორფომეტრული კვლევა
eleqtronul suraTebze β-ujredebis da insulinis granulebis
raodenobis, procentuli Semadgenlobis, diametris da farTobis
gasazomad gamoviyeneT Adobe Photoshop CC. zomebis gadasayvanad
piqselebidan mikrometrebSi vxemZRvanelobdiT Semdegi formuliT (M X N
/10000) X K, M aris mikroskopis obieqtivis gadideba, gamosaxuli
piqselebSi, K aris TviTon suraTis resolution (piqseli/sm-ze), N TviTon
suraTis gadidebaa (suraTis sigrZe sm. gamravlebuli resolution-ze
rezoluciaze da gayofili monitorze gamosaxuli suraTis gadidebaze
anu 100 %, 10000 ki aris sm-Si mikrometrebis raodenoba. gamoTvlebiT
miviReT rom 41 piqseli tolia 11 µm-isa. Ddazomvebi vawarmoeT am
monacemebis mixedviT. monacemebis statistikuri damuSavebisaTvis
gamoviyeneT IBM SPSS Statistics 20.
28
იმუნოჰისტოქიმიური კვლევა
gamosakvlevi masalis fiqsacia warmoebda 10% formalinis buferul
xsnarSi (Ph 7,2-7,3) 10sT-is ganmavlobaSi, ris Semdegac qsovilis nimuSebs
vayalibebdiT parafinSi. imunohistoqimiuri kvlevisaTvis 3-4mk sisqis
anaTlebis deparafinizacia tardeboda standartuli wesiT. pirveladi
antisxeulebis saxiT gamoyenebuli iyo specifikuri antisxeulebi Mouse
Monoclonal CK19 (clone RCK108,1:50 dilutionDAKO), Mouse Monoclonal Endothelial Cell
Marker CD34 (clone QBEnd/10, dilution 1;100,DAKO),and guinea pig anti-swine insulin
antibody( dilution 1:100 DAKO,Carpinteria, CA,USA ), vizualizaciis sistemis
saxiT gamoyenebuli iyo sistemaAABC Staining System („DAB Novocastra“),
birTvebi damatebiTad iRebeboda harisis hematoqsilinis wyalxsnariT.
kontrolis saxiT viyenebdiT mwarmoeblis mier rekomendirebul
SeRebvas pirveladi antisxeulebis gareSe araspecifikuri reaqciis
gamoricxvis mizniT.
ელექტრონul-რადიოავტოგრაფული და რადიოიმუნური კვლევა
kortikosteronis (B),Bsomatotropinis (CTG), sasqeso steroidebis
(T,E2) gansazRvra warmoebda radioimunologiurad komerciuli (Kit)
krebulis gamoyenebiT.AvirTagvebis pankreasSi androgenebis
receptorebis (AR) gamosavlenad dakvlis win 1 saaTiT adre
intraperitonealurad Segvyvavda sinTezuri radioaqtiuri androgen-
meTiltrienoli (R-1881). dakvlis Semdeg masalis nawils vwonidiT da
homogenizaciis Semdeg vaTavsebdiT scintilaciur siTxeSi.
radiometruli kvlevisaTvis gamoyenebuli iyo aparati ”Бета”. masalis
meore nawili muSavdeboda radioavtografiis klasikuri meTodiT.
moniSnuli struqturebi-androgen receptorebi (AR) iTvleboda 900
gadidebaze. Ppankreasis biosinTezuri aqtivoba isazRvreboda dnm-is da
29
rnm-is sinTezis doniT. eleqtrono radioavtografuli kvlevisaTvis
qsovilis 1X0,5 mm zomis naWrebi Tavsdebოდა penicilinis boTlebSi 5 ml
are 199,1 % xbos SratSi. Semdeg Segvyavda dnm-isa da rnm-is radioaqtiurი
winamorbedები da tardebოდა inkubacia TermostatSi 380C temperaturaze
90 wT-is ganmavlobaSi. inkubacia warmoebდა gancalkevebulad dnm-is (20
mk.Ki/ml H3-TimidiniT fardobiTi aqtivoba 21.6 Ki/mM) da rnm-is (40
mk.Ki/ml. H3-uridiniT, fardobiTi aqtivoba 24 Ki/mM) radoaqtiuri
winamorbedebiT. inkubaciis dasrulebis Semdeg qsovilis naWrebs
vavlebdiT civ mkvebav areSi, homogenizaciis Semdeg vaTavsebdiT
scintilaciur siTxeSi. radioaqtivobis daTvla xdeboda aparat ‘‘Бета”-s
meSveobiT.
სტატისტიკური ანალიზი
monacemebis maCveneblebs Soris gansxvavebis sandoobis Sesamowmeblad
gamoyenebuli iqna stiudentis kriterumi T.
30
გამოკვლევის შედეგები
ვირთაგვების პანკრეასის მორფო-ფუნქციური თავისებურებანი ალოქსანური დიაბეტის
დროს
intravenurad aloqsanis diabetogenuri dozis Seyvanis Semdeg
virTagvebSi aRiniSneba glukozis mrudis cvlilebis ramodenime faza.
pirveli faza: hiperglikemiuri, romelic maqsimums aRwevda pirveli 2-4
saaTis ganmavlobaSi. zogierT virTagvaSi hiperglikemiuri faza
elviseburad gadadioda hiperglikemiurSi, zogjer ki hiperglikemiuri
sindromi yalibdeboda mxolod aloqsanis Seyvanidan 3-4 dRis Semdeg;
meore faza: hipoglikemiuri faza_zogjer mkveTrad iyo gamoxatuli da
ZiriTadad vlindeboda 14-24 saaTis ganmavlobaSi. hipoglikemiuri
sindromis Tavidan acilebis mizniT, cxovelebs winaswar eZleodaT
tkbili wyali. sacdel cxovelebs, romlebsac glukozis raodenoba
sisxlSi hqondaT 80 mg%-ze naklebi ukeTdebodaT 40 ml. glukozis
xsnariDda bolo mesame faza myari hiperglikemiuri faza. glukozis
mrudis es cvlilebebi yovelTvis ar viTardeboda kanonzomierad,
zogjer erT-erTi faza ar iyo mkveTrad gamoxatuli. aRsaniSnavia, rom
yvela virTagva erTnairad ar reagirebda aloqsanis Seyvanaze.
eqsperimentis dawyebidan 2 kviris Semdeg sacdeli cxovelebis sisxlSi
aRiniSneboda glukozis maRali maCveneblebi (250-320 mg% da zeviT).
SemdgomSi, zogierT cxovelSi es maCvenebeli ar icvleboda da rCeboda
igive, rac adრeul vadebze. zogierT cxovelebSi glukozis koncentracia
sisxlSi matulobda (500 mg% da zeviT), maSin rodesac mTel rig
cxovelebSi is mcirdeboda arsebul maCvenebelTan SedarebiT da ar
aRemateboda 170 mg/%. iyo aseve virTagvebi, romlebsac dasawyisSiac ki ar
aReniSnebodaT Zlieri hiperglikemia. msubuqi mimdinareobis aloqsanuri
diabetis dros pirveli Tvis ganmavlobaSi glukozis raodenoba sisxlSi
iyo 130-140 mg/%. saSualo simZimis dros 170-180 mg/%. mZime aloqsanuri
diabetis dros ki glukozis Semcveloba sisxlSi aRemateboda 250 mg/%.
31
სacdeli cxovelebi myari hiperglikemiiT kargavdnen wonas,
gamoxatuli iyo poliuria, polidifsia, polifagia. mZime mimdinareobis
aloqsanuri diabetis dros aRiniSnebოდა wonis mkveTri dakleba, Tmis
cvena, dispepsiuri movlenebi (zogjer sisxliani faRaraTi), umadoba,
mkveTrad gamoxatuli sisuste. ramodenime virTagvas mZimed mimdinare
aloqsanuri diabetis dros ganuviTardaT trofiuli wylulebi.
Catarebuli histologiuri gamokvlevebis safuZvelze dadginda, rom
aloqsanis Seyvanidan 1 Tvis Semdeg pankreasis kunZulebi Secvlilia
zogi kunZuli hipertrofulia, zogi atrofirebuli, nawili kunZulebisa
Seicavs nekrozul kerebs garSemortymuls SemaerTebelqsovilovani
kafsuliT (sur. 1). kunZulebSi aRiniSnebა uweso formis fibrozuli
CanarTebi. gansakuTrebiT dazianebulia didi kunZulebi, patara
kunZulebi naklebadaa Secvlili. mZimed mimdinare aloqsanuri diabetis
dros pankreasis kunZulebis dazianebis xarisxi Rrmavdeba. pankreasis
kunZulebis meti nawili atrofirebulia. zogierT kunZulebSi β-ujredebi
ganicdian Zlier destruqciul cvlilebebs degranulacias,
vakuolizacias. gvxvdeba didi raodenobiT danekrozebuli β-ujredebi
(sur. 2), gansakuTrebiT mZimed mimdinare diabetis dros (glukoza
sisxlSi 250 mg/%-ze meti) zog kunZulSi didi nekrozuli kerebi
SemosazRvruliა SemaerTebelqsovilovani kafsuliT, xolo zogi kunZuli
Cakirulia, kalcificirebuli. mkveTrad aris gamoxatuli wilTaSua da
kunZulebTan axlo mdebare acinusebs Soris fibrozi. kunZulebSi
kolagenuri boWkoebi sxvadasxva mimarTulebiT arian ganlagebuli da
kapilaris garSemo qmnian erTgvar “muftebs.” ujredebs Soris farTo
napralebSi Cazrdili boWkoebi uxeSia da xasiaTdeba maRali
fuqsinofiliiT. pankreasis kunZulebis struqtura Zlier darRveulia.
Eeleqtronul-mikroskopuli kvlevis safuZvelze eqsperimentis
dawyebidan 1 Tvis Semdeg pankreasis kunZulebSi mZimed mimdinare
eqsperimentuli diabetis dros aRiniSneba β-ujredebis aSkara
destruqciis niSnebi, gvxdeba didi nekrozuli kerebi da apoptozuri
ujredebi (sur. 3-4). nawili β-ujredebisa SeSupebulia, maT citoplazmaSi
alag-alag gvxvdeba ganaTebuli ubnebi, an didi zonebi amovsebuli
32
gamWirvale nivTierebebiT, Cndeba vakuolebi, birTvebi naTelia, qromatini
araTanabarzomieradaa gadanawilebuli. aloqsanis Seyvanidan 1 Tvis
Semdeg β-ujredebSi adgili aqvs qromatinis kondensacias birTvis
membranis maxloblad. birTvis membranis cvlilebebs Tan axlavs misi
konturis mkveTri Semcireba. birTvebi piknozuria da danawevrebuli.
mitoqondriebi Zlier Secvlilia, osmiofiluri, wvrili, aRiniSneba
kristebis dezorganizacia. marcvlovani endoplazmuri bade
fragmentirebulia, misi membrana vakuolizirebulia sxvadasxva xarisxiT.
vakuolebisagan Tavisufal adgilebSi ribosomebi jgufebadaa
ganlagebuli. didi raodenobiTaa umwifari granulebi da lizosomebi.
mwife sekretoruli granulebis raodenoba mcirea.
insulinmaproducirebuli ujredebi ganicdian Zlier degranulacias
(sur. 5). paralelurad zemoT aRwerili β-ujredebisa am vadaze
gamovlenilia sxva tipis β-ujredebic, romelTa raodenobac, rogorc
Cans damokidebulia paTologiuri procesis simZimeze. msubuqi
mimdinareobis aloqsanuri diabetis dros (glukoza sisxlSi 130-140 mg/%)
dazianebul ujredebTan erTad gvxvdeba “naTeli” da “muqi” β-ujredebic.
umetesoba β-ujredebisa Tavisi erT-erTi polusiT uSualod exeba
kapilars. “naTel“ ujredebSi ujredSida organelebi da marcvlovani
endoplazmuri bade kargadaa ganviTarebuli da ukavia citoplazmis
mniSvnelovani nawili. marcvlovani endoplazmuri badis
cisternebisaTvis damaxasiaTebeli paraleluroba darRveulia,
cisternebis boloebi daxveulia. endoplazmuri badis membranebze
mimagrebulia ribosomebi. marcvlovani endoplazmuri badis boloebi
miqceulia goljis kompleqsisaken. β-ujredebSi goljis kompleqsi
kargadaa ganviTarebuli, misi struqturebi inarCuneben polarobas.
goljis kompleqsis “cis” boloze mravali buStukia, romlis membranebs
gaaCnia zeda nazi Sre. “trans” boloebze aRiniSneba mravalricxovani
sekretoruli granulebi, romlebic gamoirCeva dabali eleqtronuli
simkvriviT, maTSi Znelia naTeli arSiis garCeva, romelic gamoyofs
granulis SigTavss garsisagan. kapilaris diametri farToa kedeli
Txelia da gamofenilia endoTeliocitebiT, romelTa Soris
33
mravalricxovani fenestrebia, endoTeliocitebi Seicaven buStukebs.
kunZulis bazalur membranasa da kapilars Soris mWidro kontaqtia,
zogjer isini ise mWidrod arian erTmaneTTan dakavSirebuli, rom
bazaluri membrana Cans rogorc erTiani warmonaqmni. aseT ubnebSi
gamokveTili perikapilaruli sivrceebi ar vlindeba. zogierTi kunZulis
kapilarebs gorglis moyvaniloba aqvs. SemaerTebeli qsovilis raodenoba
mcirea da ar uSlis xels sekretis gadaadgilebas (sur. 6).
“muqi” tipis β-ujredebSi mitoqondriebi mcire raodenobiTaa, wvrili
zomis, uswormasworo, ganivad ganlagebuli kristebiT. mitoqondriis
matriqsi zomieri eleqtronuli simkvrivisaa. mitoqondriebi
koncentrirdebian goljis kompleqsTan. “muq“ ujredebSi sekretoruli
granulebi didi raodenobiTaa da avsebs mTel mis citoplazmas.
sekretorul granulebs sferuli moyvaniloba aqvT. mkveTradaa
gamoxatuli samfenovani membrana da eleqtronulad mkvrivi SigTavsi.
SigTavssa da membranas Soris rCeba naTeli zoli, romelsac araTanabari
sigane aqvs. Cans pinocitozuri an emiocitozuri buStukebi. xSirad erTi
sekretoruli granula ukavSirdeba meores da warmoiqmneba didi
buStukebi, ris Sedegad β-ujredebis citoplazmaSi Cndeba CaRmavebebi.
xSirad sekretoruli granulebis didi raodenoba uaxlovdeba
citoplazmur membranas da sekretoruli granulebis SigTavsi ujredSua
sivrceSi aRmoCndeba. zogierT adgilas Cans citoplazmuri badis grZeli
Sverilebi (sur. 7).
eqsperimentis 1 Tvis vadaze gvxvdeba aseve β-ujredebi, romlebSiac
mkveTrad aris gamoxatuli ujredSida organelebis momateba. adgili
aqvs intercisternuli granulebis formirebas marcvlovani
endoplazmuri badis RruebSi. marcvlovan endoplazmur badeze
mimagrebulia ribosomebi. intercisternuli granulebis SigTavsis
simkvrive SedarebiT mcirea mwife sekretoruli granulebis SigTavsis
simkvriveze. mwife granulebis raodenoba mcirea.
aloqsanis Seyvanidan 1 Tvis Semdeg pankreasSi kunZulebs gareT
gvxvdeba gardamavali tipis ujredebi. nawili am ujredebisa
moTavsebulia pankreasis sadinrebTan, nawili ki imyofeba acinusebTan
axlos, Tumca ki zRvari acinarul ujredebsa da am ujredebs Soris
34
mkveTrad aris SenarCunebuli (sur. 8). gardamavali tipis ujredebiს
umetesoba Seicavs pankreasis kunZulebis β-ujredebisaTvis
damaxasiaTebel erTeul dabali simkvrivis insulinis granulebs. aseT
ujredebs acinarul wilakSi gansxvavebuli lokalizacia aqvT. erT
wilakSi SeiZleba iyos 1-2 gardamavali tipis ujredი. am vadaze
virTagvebis pankreasSi aloqsanuri diabetis dros da sakontrolo
jgufebSi imunohistoqimiuri kvleviT, sadinrebis epiTelur ujredebis
citoplazmaSi aRiniSneba susti eqspresia CK 19-ze.
aloqsanis Seyvanidan 1 Tvis Semdeg cvlilebebi kapilarebSi ori
sxvadasxva xasiaTisaa: erTis mxriv Cans SeSupebuli endoTeluri
ujredebi, meore mxriv gamomSrali gauwylovnebuli endoTeliocitebi.
Aაseთ endoTelur ujredebSi organelebi gamomSralia, warmodgenilia
gawvrilebuli warmonaqmnebis saxiT. endoTelis plazma gafaSrebulia,
membranebi daSlili, zogjer adgili aqvs plazmolizs, ზოგ SemTxvevaSi
membranis naglejebi Cans kapilaris sanaTurSi (sur. 9). adgil-adgil
vlindeba endoTelis proliferacia. endoTelis citoplazmaSi
imunohistoqimiuri kvlevis Tanaxmad aRiniSneba susti eqspresia CD 34-ze
(sur. 10). eqsperimentis mZime mimdinareobis dros (glukoza sisxlSi 250
mg/%-ze meti), aloqsanis Seyvanidan 1 Tvis Semdeg kunZulis kapilaris
sanaTuri araTanabarzomieria, zog monakveTSi sisxlZarRvebi ara marto
gafarToebulia, aramed adgili aqvs sisxlis nakadis Senelebas, stazs.
zogierTi kapilari savsea formiani elementebiT. endoTeli gamomSralia,
gaTxelebuli, adgil-adgil kapilaris kedlis did monakveTSi aRiniSneba
endoTelis deformacia da misi gamozneqa kapilaris sanaTurSi. zogan
endoTeli Camofcqvnilia, fenestrirebuli, luminaruli zedapiri
gadasworebuliა, zogierT adgilas aRiniSneba wertilovani Caxevebi.
pinocitozi ar Cans (sur. 11). kapilaris sanaTurSi grovdeba daSlili
ujredebis, organelebis narCenebi. Eეleqtroნuli-radiavtografiiT zog
endoTelur ujredSi aღiniSneba H3–Timidinis CarTva. endoTeliocitebSi
H3–TimidiniT moniSvna Cans rogorc birTvSi, ise citoplazmaSi. erTeuli
endoTeliocitebi moiniSneba aseve H3–uridinze (sur. 12). am vadaze
adgili aqvs stromis SeSupebas, rac ganpirobebulia sisxlisZarRvebis
35
kedlis gamtarobis gazrdiT. zog perikapilarul sivrceSi gvxvdeba
amorfuli wvrilmarcvlovani masa da uxeSi kolagenuri boWkoebi,
romlebic mkveTrad osmiofiluria. yuradRebas ipyrobs kolagenuri
boWkoebi ganlagebuli kapilaris gaswvriv, romlebic Rrmad Sedian
kunZulSi, am adgilebSi kapilaris kedelSi vlindeba kaveolebi da
veziko-vakuolebi.
eqsperimentis dawyebidan 1 Tvis Semdeg aRiniSneba perikapilaruli
sivrcis da kunZulis Zlieri infiltracia makrofagebiT, plazmocitebiT,
fibroblastebiT (sur. 13). gvxvdeba erTeuli limfocitebic.
gansakuTrebiT yuradRebas iqcevs makrofagebi. makrofagebs aqvT sferuli
forma, birTvi ufro xSirad wargrZelebulia, zogjer mrgvali,
citoplazma marcvlovania. kargad aris ganviTarebuli marcvlovani
endoplazmuri bade. is ZiriTadad Sedgeba milakebisagan, romlebzedac
bevri ribosomaa. did momwifebul makrofagebSi marcvlovani
endoplazmuri bade gansakuTrebulad kargad aris ganviTarebuli, kargad
Cans goljis kompleqsic, romelic warmodgenilia brtyeli cisternebiT
da wvrili buStukebiT. aseT makrofagebSi zogjer Cans kontaqti
granularul da agranularul endoplazmur badeebs Soris.
citoplazmaSi sxvadasxva zomis da simkvrivis lizosomebia. makrofagebSi
vlindeba cximis wveTebi da daSlili ujredebis narCenebi. makrofagebs
gaaCniaT sxvadasxva zomis wanazardebi _ fsevdopodiebi. makrofagebi
moiniSneba rnm-is winamorbediT. makrofagebi H3-TimidiniT ar moiniSnebian
(sur. 14).
eqsperimentis erTi Tvis vadaze msubuqi mimdinareobis aloqsanuri
diabetis dros gansakuTrebiT bevria dabaldiferencirebuli da
axalgazrda fibroblastebi. momwifebuli fibroblastebi iSviaTad
gvxvdeba. dabaldiferencirebul fibroblastebs aqvT mrgvali birTvi da
SedarebiT martivi organizacia. proliferaciis adreul stadiaze
fibroblastebi saSualo zomisaa, aqvT varskvlaviseburi moyvaniloba.
maTSi marcvlovani endoplazmuri bade warmodgenilia mcire milakebiT
da cisternebiT, mravlad gvxvdeba ribosomebi da polisomebi,
mitoqondriebi gansxvavebuli zomisaa. dabaldiferencirebul
fibroblastebSi goljis kompleqsi sustad aris gamoxatuli.
36
marcvlovani endoplazmuri bade warmodgenilia milakovani cisternebiT,
romlebic ujredis sigrZivi RerZisakenaa orientirebuli. didi
raodenobiTaa Tavisufali ribosomebi. yuradRebas iqcevs vezikulebi da
pinocitozuri buStukebi. didi raodenobiTaa Tavisufali mitoqondriebi,
kristebis Cveulebrivi ganlagebiT. aseve vlindeba naTeli mitoqondriebi
mokle kristebiT. eleqtronul-radioavtografiuli meTodiT
dabaldiferencirebuli da axalgazrda fibroblastebi intensiurad
moiniSneba H3-TimidiniT, erTeuli fibroblastebi moiniSneba H3-uridinze.
mZimed mimdinare paTologiuri procesis dros gvxdeba sxvadasxva
simwifis fibroblastebi. dabaldiferencirebuli, axalgazrda
fibroblastebi cotaa. aRiniSneba mwife fibroblastebis didi raodenoba.
mwife kolagenmaproducirebel fibroblastebs kargad aqvT
ganviTarebuli endoplazmuri bade, is TiTqmis ikavebs mTel
citoplazmas da ujredi mogvagonebs Rrubels. goljis kompleqsi
nawilobriv reducirebulia. marcvlovani endoplazmuri badis
cisternebi xSirad erwymian citoplazmis membranas. eleqtრონul -
radiografiuli kvleviT fibroblastebi ar moiniSneba H3-Timidinze,
Tumca mkveTrad moiniSnebian H3-uridinze.
am vadaze didi raodenobiTaa plazmuri ujredebic eqscentrulad
ganlagebuli mrgvali an ovaluri birTviT, msxvili birTvakiT.
citoplazmaSi vlindeba mitoqondriebi, goljis kompleqsi, Cans
marcvlovani endoplazmuri badis niSnebi. arsebuli plazmuri ujredebi
არ moiniSneba Timidinis winamorbediT, Tumca sakmaod intensiuria
moniSvna H3-uridiniT.
eqsperimentis dawyebidan 1 Tvis Semdeg msubuqad mimdinare
aloqsanuri diabetis dros gvxvdeba mcire zomis limfocitebi.
limfocitebi osmiofiluria, rac ganapirobebs am populaciis muq fers.
birTvebi mrgvalia, birTvis membranaSi aRiniSneba invaginaciebi.
birTvakebi ar vlindeba, an moTavsebulia eqscentrulad da erwymis
birTvis heteroqromatinis grovebs. citoplazma osmiofiluria da
Sevsebulia mravalricxovani ribosomebiT. erTeul wvril mitoqondriebs
aqvT mkvrivi matriqsi. marcvlovani endoplazmuri badis cisternebi ar
Cans. eleqtrono-radioavtografiulma kvlevam gviCvena, rom patara
37
limfocitebis birTvebi moiniSneba H3-TimidiniT (sur. 15). aloqsanis
Seyvanidan 1 Tvis Semdeg, mZimed mimdinare paTologiuri procesisas
Cndeba saSualo da didi zomis limfocitebი. eleqtronul-
radioavtografiuli kvleviT saSualo da didi limfocitebi mkveTrad
moiniSneba H3-uridiniT. H3-uridini vlindeba birTvsa da citoplazmaSi.
vercxlis marcvlebi jgufebis saxiT ganlagebulia hetero da
euqromatinis sazRvarze. vercxlis marcvlebi citoplazmaSi metia,
vidre birTvze. gvxvdeba aseve muqi limfocitebi, romlebic
garSemortymuli arian naTeli qobiT. xSirad aseTi limfocitebi
imyofebian mWidro kontaqtSi endokrinul ujredebTan.
eqsperimentis dawyebidan 1 Tvis Semdeg α da δDujredebi
gadanacvlebulia kunZulis centrisaken (sur. 16). naxevrad Txel
anaTalze ujredebi dagrZelebulia. gazrdilia kontaqti α da
δDujredebs Soris. kerZod, msubuqi mimdinarebis aloqsanuri diabetis
dros (glukoza sisxlSi 170 mg/%) pankreasis kunZulebis α ujredebSi
sekretoruli granulebis raodenoba da SeRebvis intesioba didia, maSin
rodesac mZimed mimdinare aloqsanuri diabetis dros (glukoza sisxlSi
250 mg%) sekretoruli granulebis raodenoba Seucvlelia an
umniSvnelod matulobs. pankreasis kunZulebis α tipis ujredebi
ZiriTadad gvxvdeba kunZulis periferiul nawilSi, magram zogi maTgani
gadanacvlebulia centrisaken. Eeleqtroნul mikroskopuli kvleviT α
ujredebs aqvT ovaluri an poligonaluri forma. ujredebis citoplazma
dabali eleqtronuli simkvrivisaa, ujredSida organelebis simciris
gamo. marcvlovani endoplazmuri bade warmodgenilia mcirericxovani
cisternebiT, romlebzedac ribosomebi iSviaTadaa mimagrebuli.
citoplazmaSi gvxvdeba Tavisufali ribosomebi da poliribosomebi.
citoplazmis umniSvnelo nawili ukavia goljis kompleqs. goljis
kompleqsi warmodgenilia cisternebiT, mcire zomis vezikulebiT da
formirebadi sekretoruli granulebiT, romlebic dabali eleqtronuli
simkvrivisaa. mitoqondriebi cotaa, patara zomis, aqvT amodrekili
mTvarisebri forma, kristebis raodenoba mcirea da TviT mitoqondriebi
gabneulia mTel citoplazmaSi. sekretoruli granulebi sferuli
38
formisaa da dafarulia uwyveti samSriani membraniT. ujredebis SigTavsi
maRali eleqtronuli simkvrivisaa osmiofilobis gamo, bevria
hipergranulirebuli α ujredi. sekretoruli granulebi Tavisi
simravlis gamo avseben mTel citoplazmas. aseTi α ujredebis raodenoba
matulobs procesis simZimis proporciulad (glukoza sisxlSi 250 mg%-
ze meti).
eqsperimentis dawyebidan 1 Tvis Semdeg pankreasis kunZulebis δD
ujredebi uswormasworo an poligonaluri formisaa, zogi kunZulis
centrSia, zogi ki mcire raodenobiT periferiaze. momatebulia maTi
Sexebis zedapiri pankreasis kunZulebis α da β ujredebTan. eleqtroნul
-mikroskopuli kvlevis safuZvelze δDujredebis birTvi didia, masSi
qromatini Tanabrad aris gadanawilebuli. gvxvdeba ubnebi, sadac
sWarbobs euqromatini. marcvlovani endoplazmuri bade mcire
raodenobiTaa warmodgenili. organelebi xSirad polarulad aris
ganlagebuli. mravalricxovani sekretoruli granulebi moqceulia
sisxlaZarRvovani polusisaken. goljis kompleqsi kargad aris
ganviTarebuli da warmodgenilia mokle cisternebiT da
mravalricxovani vezikulebiT. goljis kompleqsis maxloblad xSirad
gvxvdeba formirebadi-sekretoruli granulebi. mitoqondriebi mcire
raodenobiT Seicavs wvril, momrgvalo-ovaluri, zogjer araswori
formis kristebs. iSviaTad gvxvdeba sekretoruli granulebi-mrgvali,
ovaluri formis, mkveTrad SemosazRvruli membraniT, romelic adgil-
adgil wyvetilia. membranis wyvetil adgilebSi granulebis SigTavsi
uSualo kontaqtSia hialoplazmasTan. δ ujredebis granulebis SigTavsis
simkvrive α da β ujredebis granulebis SigTavsis simkvriveze dabalia.
ujredebis granulebis simkvrive erTi da igive ujredSic ki SeiZleba
sxvadasxva iyos. granulebis SigTavssa da maT garss Soris sivrce
imdenad mcirea, rom eleqtronogramaze arc ki Cans.Ppankreasis
kunZulebis δ ujredebSi aloqsanuri diabetis msubuqi mimdinareobis
dros (glukoza sisxlSi 170 mg%-ze meti), granulebis raodenoba
umniSvnelod momatebulia, maSin rodesac aloqsanuri diabetis mZime
39
mimdinareobis dros (glukoza sisxlSi 250 mg/%-ze meti) mkveTrad
matulobs.
40
დანართი 1
suraTebi
sur. 1. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZulebi. zogi kunZuli atrofirebulia, zogi
hipertrofirebuli. nawili kunZulebisa Seicavs nekrozul kerebs,
garSemortymuls SemaerTebelqsovilovani kafsuliT.Hhematoqsilin
eozini X20.
41
sur. 2. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZuli. aRiniSneba β-ujredebis nekrozi.
hematoqsilin eozini X40.
42
sur. 3. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZuli. Ddidi nekrozuli kerebi. eleqtronuli
mikroskopia X9000.
43
sur. 4. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZuli. didi raodenobiTaa apoptozuri
ujredebi. eleqtronuli mikroskopia X12000.
44
sur. 5. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZuli. β-ujredSi mwife sekretoruli
granulebi. β-ujredebi ganicdian Zlier vakuolizacias, degranulacias.
eleqtronuli mikroskopia X10000.
45
sur. 6. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZuli. zogierTi kunZulis kapilarebs
gorglis moyvaniloba aqvs. SemaerTebeli qsovilis raodenoba mcirea.
eleqtronuli mikroskopia X9000.
46
sur. 7. aloqsanuri diabeti. virTagvebis pankreasi aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZuli. სekretoruli granulebis didi
raodenoba uaxlovdeba citoplazmur membranas. sekretoruli granulebis
SigTavsi ujredSua sivrceSia. zogierT adgilas Cans citoplazmuri
badis grZeli Sverilebi X6000.
47
სურ. 8. aloqsanuri diabeti virTagvas pankreasi. aloqsanis Seyvanidan 1
Tvis Semdeg. gardamavali tipis ujredebi. nawili am ujredebisa
moTavsebulia pankreasis sadinrebTan, nawili ki imyofeba acinusebTan
axlos, Tumca ki zRvari acinarul ujredebsa da am ujredebs Soris
mkveTrad aris SenarCunebuli. ეleqtroნuli-radiavtografiა. naxevarad
Txeli anaTali X1500.
48
sur. 9. aloqsanuri diabeti. virTagvas pankreasi. aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZuli. sinusoidebis endoTelis plazmolema
gafaSrebulia, membranebi daSlili. adgili aqvs plazmolizs. zog
SemTxvevaSi membranis naglejebi Cans kapilaris sanaTurSi. eleqtronuli
mikroskopia X6000.
49
sur. 10. aloqsanuri diabeti. daavadebuli virTagvas pankreasi aloqsanis
Seyvanidan 1 Tvis Semdeg. pankreasSi aRiniSneba susti eqspresia CD-34-ze.
imunohistoqimia X40.
50
sur. 11. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZuli. zogierTi kapilari savsea formiani
elementebiT. endoTeli Camofcqvnilia, fenestrirebuli, luminaruli
zedapiri gadasworebuliა, zogierT adgilas aRiniSneba wertilovani
Caxevebi. pinocitozi ar Cans. eleqtronuli mikroskopia X6000.
51
sur. 12. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZuli. erTeuli endoTeliocitebi moiniSneba
H3–uridinze. eleqtronuli radioavtografia X6000.
52
sur. 13. aloqsanuri diabeti. virTagvebis pankreasi aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZuli. aRiniSneba perikapilaruli sivrcis da
kunZulis Zlieri infiltracia makrofagebiT, plazmocitebiT,
fibroblastebiT. eleqtronuli mikroskopia X6000.
53
sur. 14. aloqsanuri diabeti. virTagvebis pankreasi aloqsanis Seyvanidan
1 Tvis Semdeg. pankreasis kunZuli. makrofagi mkveTrad moiniSneba H3-
uridinze. eleqtronuli radioavtografia X9000.
54
sur. 15. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZuli. limfocitis birTvi moiniSneba H3-
TimidiniT. eleqtronuli radioavtografia X9000.
55
sur. 16. aloqsanuri diabeti. virTagvas pankreasi aloqsanis Seyvanidan 1
Tvis Semdeg. pankreasis kunZuli. Aα da δD ujredebi gadanacvlebulia
kunZulis centrisaken. pankreasis kunZulis α ujredebSi sekretoruli
granulebis raodenoba didia. eleqtronuli mikroskopia X6000.
56
მორფოლოგიური ცვლილებები ვირთაგვების პანკრეასში
ალოქსანური დიაბეტის დროს და პლაფერონის ზემოქმედების
შემდეგ
aloqsanuri diabetis dawyebidan 1 Tvis da plaferonis 10 dRiani
kursis Semdeg aloqsan-plaferonis jgufis virTagvebSi glukozis
Semcveloba sisxlSi mcirdeba 50-60 mg% aloqsanur jgufTan SedarebiT,
Tumca ki metia sakontrolo jgufis virTagvebis glukozis donesTan.
glukozis donis cvlilebebi sisxlSi eqsperimentul da sakontrolo
jgufebSi damuSavebulia statistikurad da moyvanilia cxrilebSi (cxr.
1 da 2) (grafa 1).
aloqsan-plaferonis jgufSi virTagvebis wona aloqsanur jgufis
virTagvebis wonasTan SedarebiT Secvlili ar aris. pankreasis
kunZulebSi mniSvnelovani cvlilebebi ar aRiniSneba. Hhistologiurad
kunZulebi sxvadasxva zomisaa. zogi kunZuli hipertrofulia,
hiperemiulia, zogic atrofirebuli (sur. 17). rigi kunZulebis struqtura
darRveulia. pankreasis kunZulebis β-ujredebSi nekrobiozuli
cvlilebebis paralelurad gvxdeba erTeuli ujredebi, romlebSic
aRiniSneba mitozebi. vizualurad apoptozuri ujredebis raodenoba
Semcirebulia. aloqsan-plaferonis jgufis virTagvebis pankreasis
kunZulebSi kapilarebis endoTeli Txelia, kargad fenestrirebuli.
pankreasis kunZulebSi gvxvdeba bevri axlad warmoqmnili kapilari (sur.
18). imunohistoqimiuri kvlevis safuZvelze aloqsan-plaferonis jgufis
virTagvebis pankreasSi aRiniSneba CDD34-is Zlieri eqspresia kunZulebis
kapilarebis endoTelis citoplazmaSi (sur. 19). CD 34-is mimarT
imunoreaqtiuloba kunZulebSi da sadinrebis momijnave ujredebSi
maRalia. aloqsan-plaferonis jgufis virTagvebis pankreasSi CD 34-is
Semcveli pozitiuri ujredebi gabneulia mTel pankreasSi (sur. 20), maSin
rodesac aloqsanis da sakontrolo jgufis virTagvebis pankreasSi CD
34-is eqspresia sakmaod SezRudulia (sur. 21).
57
aloqsan-plaferonis jgufis virTagvebis pankreasSi perikapilaruli
sivrce gaganierebulia. fibrozuli CanarTebi mcire raodenobiTaa,
kolagenuri boWkoebi Txelia. perikapilarul sivrceSi da momijnave
qsovilebSi aRiniSneba makrofagebis, lifocitebis, plazmocitebis da
erTeuli fibroblastebis infiltracia. gansakuTrebul interess iwvevs
makrofagebi, eqscentrulad ganlagebuli didi birTviT. citoplazmaSi
kargad Cans ribosomebi, vakuolebi, fagocitebi, polisomebi da
lizosomebi. granularuli endoplazmuri bade Txelia da warmodgenilia
cisternebiT da vakuolebiT, romlebic axlos arian birTvTan.
makrofagebSi mitoqondriebi didi raodenobiTaa. makrofagebi intesiurad
moiniSnebian H3-Timidinze da H
3-uridinze (sur. 22).
aloqsan-plaferonis jgufis virTagvebis pankreasSi gansakuTrebul
yuradRebas ipyrobs gardamavali tipis β-ujredebis niSan Tvisebebis
Semcveli erTmaneTisagan gansxvavebuli ujredebi (sur. 23). am
gardamavali tipis ujredebs pankreasSi aqvT sxvadasxva lokalizacia.
nawili am ujredebisa moTavsebulia acinusebTan axlos, Tumca ki
sazRvari acinarul ujredebsa da gardamavali tipis ujredebs Soris
mkveTrad aris SenarCunebuli. nawili ujredebisa gvxdeba wilSida,
interlobulur da intralobulur sadinrebTan. wilSida sadinrebTan
arsebuli gardamavali tipis ujredebis apikaluri polusi aRwevs
sadinris sanaTurs, ujredis ZiriTadi masa ki moTavsebulia acinusis
bazalur nawilTan. აloqsan-plaferonis jgufis virTagvebis pankreasSi
gardamavali tipis ujredebi imyofebian diferenciaciis da simwifis
sxvadasxva xarisxSi da mdgomareobaSi. imunohistoqimiuri kvlevis
safuZvelze CK 19-is eqspresia aRiniSneba pankreasSi arsebul sadinrebis
epiTelur ujredebis citoplazmaSi (sur. 24). anti CK 19-ze iRebeba
wvrili, interlobuluri da intralobuluri sadinrebis ujredebi. CK
19-is eqspresia ZiriTadad vlindeba pankreasis kunZulebTan axlos myofi
sadirebis epiTeluri ujredebis citoplazmaSi. gansakuTrebiT Zlieri
eqspresiaa ujredis bazalur nawilSi. CK 19-is susti eqspresia vlindeba
acinarul ujredebSi da TiTqmis ar aris kunZulebis ujredebSi.
insulinis granulebis SeRebvis intensioba cvalebadia da ZiriTadad
58
ufro mkveTria kunZulebis axlos arsebul sadinris epiTelur
ujredebSi. eleqtronogramaze zog ujredSi insulinis granulebis
raodenoba mcirea, zogierT ujredebSi ki bevri da Sesabamisad
aRiniSneba cvalebadi intesiobis SeRebva anti insulinze (sur. 25).
eleqtronogramaze zogi gardamavali tipis ujredi Seicavs
acinarul da β-ujredisaTvis damaxasiaTebel niSnebs (sur. 26). aseTi
gardamavali tipis ujredebis erTi polusi miqceulia kunZulisaken და
Seicavs β-ujredebisaTvis damaxasiaTebel granulebს mkveTrad
gamoxatuli garsiT, kerZoT mkvrivi guliT da asimetriuli naTeli
arSiiT. citoplazmis es monakveTi dabali eleqtronuli simkvrivisaa,
vinaidan is Tavisufalia organelebisagan. marcvlovani endoplazmuri
badis cisternebs ara aqvT egzokrinuli ujredebisaTvis damaxasiaTebeli
paraleluroba da warmodgenilia vezikulebiT. mokle cisternebi
erTmaneTSia gadaxlarTuli, ribosomebi mcire raodenobiTaa. zogierT
ujredSi marcvlovani endoplazmuri bade vlindeba CanarTis saxiT,
swored am ubnebSi didi raodenobiTaa β-insulocitebis granulebi,
mitoqondriebi wvrilia, Seicavs erTeul kristebs da naTel matriqs, rac
aseve damaxasiaTebelia β-ujredebisaTvis. citoplazmis sxva ubnebSi
SenarCunebulia marcvlovani endoplazmuri badis cisternebis
paraleluroba, amave dros mitoqondriebi msxvili, momrgvalo-ovaluri
formisaa, gaaCnia eleqtronulad mkvrivi matriqsi da mravalricxovani
kristebi, aqve vlindeba zimogenuri granulebi e.i. yvelaferi is rac
damaxasiaTebelia egzokrinuli ujredebisaTvis (sur. 27).
ეleqtronogramaze nawili ujredebisa moTavsebulia acinusებTan axlos
da Seicavs pankreasis kunZulebis β-ujredebisaTvis damaxasiaTebel
granulebs, romlebic imyofebian perinuklearul zonaSi an kidev
ujredis erT erT polusTan. am ujredebis birTvs gardamavali
(Sualeduri) agebuleba aqvs, kerZod qromatinis masaSi sWarbobs
euqromatini. imunohistoqimiuri kvlevis safuZvelze aloqsan-plaferonis
jgufis virTagvebis pankreasis erTeuli acinaruli ujredebi iRebeba
anti insulinze. insulinis granulebis SeRebvis intesioba cvalebadia da
ZiriTadad ufro mkveTria kunZulebis axlos.
59
eleqtronogramaze pankreasis kunZulebSi Zalian iSviaTad gvxvdeba
gardamavali tipis ujredebi, romelic erTdroulad Seicaven
α-ujredebisaTvis damaxasiaTebel glukagonis da β-ujredebisaTvis
damaxasiaTebel erTeul insulinis granulebs (sur. 28).
60
დანართი 2
suraTebi
sur. 17. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).
virTagvas pankreasi. pankreasis kunZulebi. zogi kunZuli hipertrofulia,
hiperemiulia, zogic atrofirebuli. hematoqsilin eozini X40.
61
sur. 18. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).
virTagvas pankreasi. pankreasis kunZulebSi gvxvdeba bevri axlad
warmoqmnili kapilari. eleqtronuli mikroskopia X6000.
62
sur. 19. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).
virTagvas pankreasi. kunZulebis kapilarebis endoTelis citoplazmaSi
aRiniSneba CDD34-is Zlieri eqspresia. imunohistoqimia X40.
63
sur. 20. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).
virTagvas pankreasi. CD 34-is Semcveli pozitiuri ujredebi gabneulia
mTel pankreasSi. imunohistoqimia X40.
64
sur. 21. aloqsanisa da sakontrolo jgufis virTagvebis pankreasi. CD 34-
is eqspresia sakmaod SezRudulia. imunohistoqimia X40.
65
sur. 22. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).
virTagvas pankreasi. makrofagi intesiurad moiniSneba H3-Timidinze da H
3-
uridinze. eleqtronuli radioavtografia X14000.
66
sur. 23. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).
virTagvas pankreasi. gardamavali tipis ujredebi. nawili ujredebisa
gvxdeba wilSida, interlobulur da intralobulur
sadinrebTan.Eeleqtronuli radioavtografia. naxevrad Txeli anaTali
X1500.
67
sur. 24. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).
virTagvas pankreasi. CK 19-is Zlieri eqspresia pankreasis kunZulebTan
axlos myof sadinrebis epiTelur ujredebis citoplazmaSi.
imunohistoqimia X40.
68
sur. 25. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).
virTagvas pankreasi. pankreasis kunZulebTan axlos myofi sadirebis
epiTelur ujredebSi aRiniSneba cvalebadi intesiobis SeRebva anti
insulinze. imunohistoqimia X40.
69
sur. 26. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).
virTagvas pankreasi. Aacino-insularuli ujredi. Uujredi Seicavs β-
ujredebisaTvis damaxasiaTebel insulinis maproducirebel, aseve
acinaruli ujredebisaTvis damaxasiaTebel zimogenur granulebs.
eleqtronuli mikroskopia X9000.
70
sur. 26. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).
virTagvas pankreasi. acino-insularuli ujredi. ujredi Seicavs β-
ujredebisaTvis damaxasiaTebel insulinis maproducirebel granulebs,
citoplazmis sxva ubanSi SenarCunebulia marcvlovani endoplazmuri
badis paraleluroba. eleqtronuli mikroskopia X12000.
71
sur. 28. aloqsanuri diabeti da plaferoni (eqsperimentis me-40 dRe).
virTagvas pankreasi. gardamavali tipis ujredi erTdroulad Seicavs α-
ujredebisaTvis damaxasiaTebel glukagonis da β-ujredebisaTvis
damaxasiaTebel erTeul insulinis granulebs. eleqtronuli mikroskopia
X6000.
72
cxrili 1. glukozis da insulinis Semcveloba virTagvebis sisxlSi aloqsanuri diabetis dros, plaferonis
Syvanamde da plaferonis Seyvanis Semdeg.
ჯგუფი საშუალო
მაჩვენებელი
სტანდარტული
გადახრა
კორელაციის
კოეფიციენტი r
სტიუდენტის
კრიტერიუმი t
სანდოობა
p
glukoza პლაფერონის
შეყვანამდე
211.57 12.18 r =0.732 p=0.000
18.160
0.000
glukoza პლაფერონის შეყვანის
შემდეგ
172.29 6.16
საკონტროლო ჯგუფი 80.86 8.51
insulin plaferonis Seyvanamde
5.81 0.24
insulini plaferonis Seyvanis Semdeg
9.16 0.22
sakontrilo jgufi 25.46 0.34
gansxvaveba statistikuradDsandoa (t=18.160; p=0.000)
plaferonis Seyvanis Semdeg standartuli gadaxris mniSvneloba sakmaod dabalia, rac efeqtis erTgvarovnebaze
metyvelebs. korelaciis koeficientis dadebiTi mniSvneloba miuTiTebs imaze, rom yvela SemTxvevaSi aRiniSneba
dadebiTi efeqti. saSualo maCveneblebs Soris gansxvavebis sandoobis Sesamowmeblad gamoyenebul iqna stiudentis
kriteriumi t. amasTanave, sakontrolo jgufebis Sedarebisas stiudentis kriteriumi iyo ori damoukidebeli
SerCevisaTvis.
73
cxrili 2. საშუალო მაჩვენებლების (N=10) განაწილება დღეების მიხედვით.
grafa 1. insulinis Semcveloba sisxlSi.
74
ალოქსან-პლაფერონის ჯგუფის ვირთაგვების პანკრეასში
კუნძულ გარეთ არსებული იზოლირებული β-უჯრედები და
მათი ფუნქციური მდგომარეობის შეფასება ელექტრონულ-
მორფომეტრული მეთოდით
zogierTi kunZulgareT arsebuli β-ujredebi izolirebulia da ar
aris organizebuli kunZulebSi. sazRvari am ujredebsa da acinusebs
Soris mkveTrad aris gamoyofili. es ujredebi Seicavs β-ujredebisaTvis
damaxasiaTebel insulinis granulebs. Aam tipis β-ujredebSi kargad
vlindeba, rogorc naTeli, aseve muqi insulinis granulebi. muqi
insulinis granulebi warmodgenilia mkvrivi guliT da garSemo TeTri
haloTi, maSin rodesac naTel granulebs gaaCniaT eleqtrono naTeli
guli da TeTri halo. insulinis granulebis umetesoba moTavsebulia
perinuklearul zonaSi (sur. 29). Aam β-ujredebis birTvi didia da masSi
sWarbobs euqromatini. Cvens mier eqstra insularul komponentaT
miCneuli iyo is izolirebuli ujredebi, romlebSiac kargad vlindeboda
birTvi da mwife insulinis granulebi. swored am ujredebis funqciuri
mdgomareobis gansasazRvrad vawarmoeT β-ujredebSi insulinis
granulebis raodenobis, diametris, farTis, naTeli da muqi granulebis
procentuli Sesabamobis gansazRvra da Sedareba aloqsanuri da
sakontrolo jgufis virTagvebis pankreasis kunZulebis β-ujredebis
Sesabamis parametrebTan erTi da igive zomis fragmentebSi. miRebuli
monacemebis safuZvelze dadginda rom aloqsan-plaferonis jgufis
virTagvebis pankreasis izolirebul β-ujredebSi insulinis granulebis
raodenoba naklebia, vidre aloqsanis da sakontrolo jgufis
virTagvebis pankreasis kunZulebis β-ujredebSi. aloqsan-plaferonis
jgufSi naTeli insulinis granulebis procentuli raodenoba metia,
xolo muqis naklebia aloqsanur da sakontrolo jgufTan SedarebiT.
samive jgufis β-ujredebSi sxvaoba insulinis granulebis diametrSi ar
75
aRiniSneba. miRebuli monacemebi damuSavebulia statistikurad da
moyvanilia cxrilSi (cxrili 3).
76
დანართი 3
suraTebi
sur. 29. aloqsanuri diabeti da plaferoni. kunZul gareT arsebuli
izolirebuli β-ujredi.insulinis granulebis umetesoba moTavsebulia
perinuklearul zonaSi. eleqtronuli mikroskopia X9000.
77
cxrili 3. insulinis granulebi virTagvebis pankreasSi aloqsan-plaferonis jgufis izolirebul β-ujredebSi da
aloqsanur da sakontrolo jgufis pankreasis kunZulebis β-ujredebSi.
gansxvaveba statistikuradDsandoa *(p<0.0001)
ჯგუფი ფართობი ინსულინის
გრანულების
რაოდენობა
მუქი
ინსულინის
გრანულების
რაოდენობა
ნათელი
ინსულინის
გრანულების
რაოდენობა
მუქი
ინსულინის
გრანულების
პროცენტული
რაოდენობა
ნათელი
ინსულინის
გრანულების
პროცენტული
რაოდენობა
მუქი
ინსულინის
გრანულების
დამეტრი (µm)
მუქი
ინსულების
გრანულების
არეა (µm2 )
ნათელი
ინსულინის
გრანულების
დიამეტრი (µm)
ნათელი
ინსულინის
გრანულების
არეა (µm2)
I -
ალოქსან/პლაფერონის
ჯგუფი კუნძულ გარეთ
არსებული
იზოლირებული β-
უჯრედი
42.74
±
0.57*
113.75
±
9.55*
39.38
±
5.05*
74.38
±
5.09*
33.92
±
1.90*
66.07
±
1.90*
0.404
±
0.007*
0.143
±
0.009*
0.447
±
0.01*
0.165
±
0.007*
II –ალოქსანური
დიაბეტი ვირთაგვების
პანკრეასის
კუნძულების β-
უჯრედები
42.65
±
0.61*
136.41
±
4.74*
95.00
±
3.86*
41.00
±
2.51*
69.86
±
1.55*
30.14
±
1.55*
0.304
±
0.006*
0.076
±
0.03*
0.334
±
0.007*
0.095
±
0.04*
III - საკონტროლო
ჯგუფი ვირთაგვების
პანკრეასის
კუნძულების β-
უჯრედები
42.45
±
0.48*
344
±
0.51*
276
±
0.35*
68
±
0.71*
80.22
±
1.25*
19.78
±
1.25*
0.391
±
0.63*
0.06
±
0.05
0.397
±
0.68*
0.124
±
0.008
78
ჰორმონალურ-მეტაბოლური ცვლილებები მამრ ვირთაგვებში
ალოქსანური დიაბეტის დროს და სინთეზური რადიოინერტული
ანდროგენ მეთილტრიენოლონoს ზემოქმედების შემდეგ
meoTxe jgufis mamri virTagvebis sisxlSi aloqsanuri diabetis dros
eqsperimentis dawyebidan me-14 da 30-e dRes aRiniSneba glukozis
koncentraciis mniSvnelovani mateba, insulinis Semcvelobis kleba,
adaptaciuri hormonebis kortikosteronis (44%) da somatotropinis (38%)
mkveTri zrda, aromatizaciis procesebis aqtivacia, testosteronis
raodenobis Semcireba (52%) pankreasis β-ujredebSi dnm-isa da rnm-is (dnm-is
56%-iT, rnm-is58%-iT) sinTezis mkveTri kleba normasTan SedarebiT.
aloqsanuri diabetis dros, eqsperimentis dawyebdan 30-e dRes da or
kviriani siTezuri radioinertuli androgen-meTiltrieნolonis kursis
Semdeg virTagvebis sisxlSi glukozis koncentracia mcirdeba 23%-iT
sawyis maCvenebelTan SedarebiT. aRiniSneba kortikosteronis (27%) da
somatotropinis (75%) Semcvelobis Semcireba, aromatizaciis procesebis
aqtivaciis kleba, estradiolis da testosteronis plazmuri koncentraciis
mateba da miaxloeba normasTan (Tanafardobis koeficienti 0,008, norma
0,005). Tavisufali receptorebis Semcvelobis Semcireba 121% mde. maSin
roca sakontrolo maCvenedeli utoldeba 210%-s. dnm-isa da rnm-is sinTezis
mateba (dnm-is 16%-iT, xolo rnm-is 12%-iT). testosteronis miaxloeba
normasTan (92%) xels uwyobs androgenuli receptorebis aqtivacias,rasac
mosdevs organos mdgomareobis gaumjobeseba. pankreasis zogi kunZuli
hipertrofirebulia. aRiniSneba β-ujredebis proliferacia (sur. 30). zogi
β-ujredi aqtiurad moiniSneba dnm-iT (cxrili 4).
79
დანართი 4
cxrili 4. glukozis, insulinis (IR), testosteronis (T), estradiolis (E), kortikosteronis (K), somatotropinis (ST),
Semcveloba mamr virTagvebis sisxlSi, dnm da rnm siTezis aqtivobis cvlilebebi da androgen receptorebi pankreasis
β-ujredebSi aloqsanuri diabetis dros da siTezuri androgen meTiltrieნolonis zemoqmedebis Semdeg.
jgufebi Ddakvirvebis dReebi Gglukoza mg% IR
mkU/mg
T
ng/ml E2
ng/ml
Е2/Т ng/ml
В ng/ml
ST
ng/ml
DNA
mk.Ki/ml
RNA
mk.Ki/ml
AR
mk.Ki/ml
AR
‰
I
14
205
±
0,54*
12,74
±
0,46*
1,74
±
0,10*
0,018
±
0,002**
0,010
18,72
±
1,26*
1,26
±
0,01**
79116,9
±
12,42*
153948,5
±
22,15*
502,1
±
2,48*
19,91
±
2,01*
30
220
±
0,26*
4,82
±
0,24*
1,38
±
0,09*
0,023
±
0,003**
0,016
21,84
±
1,61*
1,98
±
0,06**
97483,3
±
24,11*
193762,8
±
15,08*
808,13
±
3,12*
33,32
±
1,64*
45
saboloo
180
±
0,84*
4,72
±
0,24**
2,41
±
0,09*
0,019
±
0,003**
0,008
20,15
±
0,90*
1,35
±
0,03**
113024,2
±
21,05*
207034,2
±
20,11*
476,9
±
1,92*
32,01
±
2,01* kontroli
125
±
0,16*
23,84
±
0,53*
2,61
±
0,23*
0,014
±
0,003*
0,005
13,00
±
1,30*
0,91
±
0,02*
141280,2
±
16,12*
265428,5
±
15,41*
394,2
±
1,42*
16,11
±
1,15*
*p=0.001 **p=0.01
80
sur. 30. virTagvაs pankreasis kunZuli. aloqsanuri diabetis dros da
sinTezuri radioinertuli androgen-meTiltrieნolonis zemoqmedebis
Semdeg ( ექსპერიმენტის 44 დღე). ჰემატოქსილინ ეოზინი X40.
81
გამოკვლევის შედეგების ანალიზი
Catarebuli kvlevis safuZvelze dadginda, rom virTagvebis pankreasis
kunZulebSi dazianebuli β-ujredebi an kapilaris garSemoa Tavmoyrili an
difuzuradaa gadanawilebuli sxva endokrinul ujredebs Soris.
sxvadasxva kunZulebSi am ujredebis raodenoba cvalebadia. gvxvdeba aseve
pankreasis kunZulebi nekrozis ubnebiT. aseTi ubnebi SemosazRvrulia
SemaerTebeli qsovilis kafsuliT. msubuqi mimdinareobis aloqsanuri
diabetis dros (glukoza sisxlSi 130-140 mg/%) eqsperimentis dawyebidan 1
Tvis Semdeg virTagvebis pankreasis kunZulebSi aRiniSneba β-ujredebis
destruqciuli cvlilebebi: degranulacia, vakuolizacia, iSviaTad
nekrozis niSnebi. amave dros aRsaniSnavia, rom ziandeba ufro didi zomis
kunZulebi, maSin rodesac patara zomis kunZulebi naklebadaa
dazianebuli. mZime mimdinareobis aloqsanuri diabetis dros (glukoza
sisxlSi 250 mg/% da meti) eqsperimentis dawyebidan 1 Tvis Semdeg
virTagvebis pankreasis kunZulovan qsovilSi β-ujredebSi insulinis
granulebi vlindeba sustad, an TiTqmis ar vlindeba, rac mowmobs am
ujredebSi insulinis totalur ukmarisobaze, e.i. maT srul gamofitvaze,
es aseve dasturdeba histologiuri, eleqtronul-mikroskopuli,
imunohistoqimiuri kvlevebiT sxva mkvlevarebis (4, 9, 11, 12, 14, 15, 17, 167-169)
mier.
ultrastruqturulma analizma saSualeba mogvca ufro TvalsaCinod
dagvedgina β-ujredebis dazianebis xarisxi da lokalizacia. Mmsubuqi
mimdinareobis aloqsanuri diabetis dros (glukoza sisxlSi 130-140mg/%) β-
ujredebi warmodgenilia ZiriTadad “naTeli” da “muqi” β -ujredebiT.
“naTel” β-ujredebSi granulebis raodenoba cotaa. gansxvavebuli zomis da
simkvrivisE granulebi gafantulia mTel citoplazmaSi, an
koncentrirebulia ujredis erT-erT polusTan. aseT β-ujredebSi
organelebi SedarebiT mcire raodenobiTaa. “muqi” β-ujredebi didi
raodenobiT Seicaven sxvadasxva zomis granulebs, romlebic
Tanabarzomieradaa gadanawilebuli mTel citoplazmaSi da iRebebian
82
gansxvavebuli intensivobiT. “muq” β-ujredebSi organelebi aseve cotaa,
mcire zomis mitoqondriebSi gvxvdeba msxvili an ramodenime kompaqturad
ganlagebuli lipiduri CanarTebi. aris ujredebis gardamavali tipic,
saSualo zomis da simkvrivis insulinis Semcveli granulebiT, romlebic
Tanabradaa gadanawilebuli mTel citoplazmaSi. amgvarad, am sami qvetipis
β-ujredebs Soris pankreasis kunZulebSi gvxvdeba aseve β-ujredebi
destruqciis aSkara niSnebiT: citoplazmis vakuolizaciiT zogierT
kunZulSi aseTi ujredebi didi raodenobiTaa.
saSualo simZimis aloqsanuri diabetis dros (glukoza sisxlSi 170-180
mg%) eleqtronul-mikroskopuli kvlevis safuZvelze β-ujredebi ganicdian
TvalsaCino destruqciul cvlilebebs, xSirad aRiniSneba citoplazmis
degranulacia, sxvadasxva xarisxiT gamoxatuli vakuolizacia. zogierT
kunZulebSi gvxdeba nekrozuli ubnebi da daSlili β-ujredebi.
kapilarebis kedeli nawilobriv gasqelebulia, perikapilaruli sivrce
gazrdilia. perikapilarul sivrceSi Cans uxeSi kolagenuri boWkoebi,
romlebic gars exvevian kapilarebs da maT garSemo qmnian “muftebs”. rac
rasakvirvelia xels uSlis sekretis gadaadgilebas.
mZime mimdinareobis aloqsanuri diabetis dros (glukoza sisxlSi 250
mg/%- ze meti), rogorc naxevrad Txel anaTlebze, ise eleqtronul-
mikroskopulad virTagvebis pankreasis kunZulebSi ZiriTadad Cans
danekrozebuli da apoptozuri β-ujredebi. amasTan erTad SenarCunebulia
erTeuli β-ujredebi destruqciis niSnebiT.
cnobilia, rom pirveli tipis diabeti xasiaTdeba pankreasis β-
ujredebis mniSvnelovani deficitiT, rac gamowveulia β-ujredebis
nekroziT da apoptoziT (7, 17, 170, 171). aloqsani gamoiyeneba specialurad β-
ujredebis dazianebisaTvis da iwvevs cxovelebSi I tipis diabetis msgavs
diabets. aloqsani azianebs β-ujredebis dnm-s da intracelularul
struqturebs, swored es aris nekrozis da apoptozis mizezi. β-ujredebSi
gazrdili apoptogenuri aqtivoba, rogorc Cans gamowveulia
mitoqondriuli membranis dazianebiT, romlis mizezs warmoadgens
intracelularuli kalciumis homeostazis moSla da mitoqondriuli
apoptozuri gzebis aqtivacia Smirnov et al. (171).
83
Catarebuli kvlevis safuZvelze unda iTqvas, rom danekrozebuli,
dazianebuli ujredebis raodenoba matulobs paTologiuri procesis
simZimis Sesatyvisad. kerZod, rac ufro mZimedaa gamoxatuli aloqsanuri
diabeti, miT ufro metia pankreasis kunZulebSi mesame jgufis ujredebi e.i.
miT ufro Rrmad arian β-ujredebi dazianebuli. amgvarad aSkaraa, rom
ZiriTad moments, romelic ganapirobebs daavadebis manifestacias, misi
mimdinareოbis simZimes aris pankreasis kunZulebis β-ujredebis dazianebis
xarisxi.
Catarebuli eqsperimentis safuZvelze pankreasis kunZulovan aparatSi
mimdinare cvlilebebis mixedviT mizanSewonilad CavTvaleT gamogveyo
Semdegi jgufebi:
I_pankreasis kunZulebSi β-ujredebi ar aris dazianebuli, an naklebad
dazianebulia;
II_pankreasis kunZulebSi mkveTrad aris gamoxatuli β-ujredebSi
destruqciis niSnebi, vlindeba ubnebi nekrozuli ujredebiT.
III_pankreasis kunZulebSi β-ujredebis umetesi nawili danekrozebulia,
vizualurad didi raodenobiT aris apoptozuri ujredebi. es cvlilebebi
da maSasadame dajgufebac pirdapir asaxavs paTologiuri procesis
simZimes.
cnobilia, rom pankreasis kunZulebSi β-ujredebi uSualo kontaqtSi
imyofebian pankreasis α da δ ujredebTan, romlebic Tavis mxriv
aproducireben hormonebs glukagons da somatostatins. aloqsanuri
diabetis sxvadasxva simZimis dros, am samive saxis ujredebis
urTierTdamokidebuleba sakmaod rTulia da moiTxovs Semdgom Seswavlas
kompleqsSi (23, 24, 26, 27, 172).
aloqsanuri diabetis dros paralelurad β-ujredebis dazianebisa,
aRiniSneba cvlilebebi pankreasis αAda δDujredebSiac. αAda δDujredebi
gadanacvlebulia centrisaken. Ggazrdilia β-ujredebis Sexebis zedapiri A
αAda δDujredebTan. ultrastruqturul doneze da SeRebviT glukagonis
granulebis Semcveloba pankreasis kunZulebis α-ujredebSi vizualurad
matulobs rogorc msubuqi, ise mZime mimdinareobis aloqsanuri diabetis
dros. mZimed mimdinare paTologiuri procesisas glukagonis granulebis
raodenoba da SeRebvis intensioba SedarebiT mcirea. amgvarad, granulebis
84
raodenobis momateba α-ujredebSi, rogorc Cans damokidebulia an
dakavSirebulia insulinis raodenobazec da mTlianad paTologiuri
procesis simZimeze. kerZod, arsebobs uSualo kavSiri insulinis
raodenobasa da glukagonis warmoqmnas Soris. cnobilia, rom glukagoni
ara marto Zlieri glikemiuri faqtoria, aramed is axdens mastimulirebel
zemoqmedebas β-ujredebis sekreciazeც (26-28), rac Tavis mxriv warmoadgens
erT-erT kompensatorul meqanizmს Saqriani diabetis dros. ar aris
gamoricxuli, rom glukagonis sekreciis gaZliereba SeiZleba iyos
dakavSirebuli insulinis kontregulaciuri funqciis amovardnasTan,
ramdenadac insulini mniSvnelovan rols TamaSobs α-ujredebis adeqvaturi
moqmedebis SenarCunebaSi W. Ham and D. Cormack (173).
aloqsanuri diabetis dros eleqtronul-mikroskopuli kvleviT
somatostatinis Semcveli granulebis raodenoba da SeRebvis intensioba δ-
ujredebSi gazrdilia. Tumca ki am momatebas gaaCnia specifikuri xasiaTi,
romelic ZiriTadad damokidebulia paTologiuri procesis simZimeze.
aloqsanuri diabetis msubuqi mimdinareobis dros somatostatinis
granulebis raodenoba δ-ujredebSi TiTqmis ucvlelia, maSin rodesac
mZimed mimdinare aloqsanuri diabetis dros vizualurad somatostatinis
granulebis raodenoba mniSvnelovnadaa momatebuli. cnobilia, rom
somatostatini amcirebs insulinis da glukagonis sekreacias, aqveiTebs
glukozis Sewovas nawlavebSi. Catarebuli eqsperimentebidan Cans
somatostatini TamaSobs mniSvnelovan rols mkveTrad gamoxatuli
glukagonis sekreciis pirobebSi, hiperglikemiis SezRudvis TvalsazrisiT.
somatostatinis es moqmedeba SeiZleba aixsnas, rogorc adgilobrivi
hormonis zemoqmedeba. rac Seexeba mis moqmedebas, rogorc namdvili
hormonisa, unda gaTvaliswinebuli iyos is faqti, rom somatostatini
warmoiqmneba ara marto δ-ujredebSi, aramed hipoTalamusis
periventrikularul da arkualur birTvebSic. somatostatinis aqtivacia
iwvevs somatotropuli hormonis daTrgunvas, rac arapirdapiri
diabetogenuri faqtoria W. Ham and D. Cormack (173). amgvarad, Sesabamisi
hormonis momateba an Semcireba kunZulis ujredebSi miuTiTebs misi
biosinTezis gaZlierebaze an Semcirebaze. eqsperimentuli diabetis dros
rigi mkvlevarebi (26, 31, 174) radioimunuri meTodis safuZvelze aRniSnaven
85
insulinis raodenobis koncentraciis Semcirebas, xolo somatostatinis
da glukagonis koncentraciis momatebas sisxlis plazmaSi.
Catarebuli eqsperimentis safuZvelze gamovlinda urTierToba erTis
mxriv insulinis Semqmnel β-ujredebsa da Sesabamisad glukagonis da
somatostatinis Semcvel αAda δ ujredebs Soris. miRebuli Sedegebis
safuZvelze SeiZleba davaskvnaT, rom pankresis kunZulebis endokrinuli
ujredebis (β, α, δ) sapasuxo reaqcia eqsperimentul diabetis pirobebSi
damokidebulia daavadebis simZimeze da rom pankreasis kunZulebis
endokrinuli nawili naxSirwylebis cvlis moSlaze pasuxobs
kompleqsurad yvela misi komponentis metnaklebi monawileobiT.
pankreasi aris rTuli maRali donis vaskuolirizaciis mqone organo.
pankreasis kunZulebs da acinarul qsovils aqvT saerTo embrionuli
warmoSoba. pankreasis arteria amaragebs rogorc pankreasis kunZulebs,
aseve acinarul qsovils. kunZulebis vaskuolirizacia xasiaTdeba Semdegi
TvisebiT: kunZulebi iReben met sisxls, vidre acinusebi; kunZulebis
sisxlZarRvebs gaaCniaT meti xveulebi da meti simkvrive; kunZulebis
kapilarebi Seqmnilia fenestrirebuli endoTeluri ujredebiT; kunZulebis
kargad ganviTarebuli vaskuლარuლi sistema ganapirobebs maT Zlier
oqsigenacias acinarul qsovilTan SedarebiT (33, 38-40).
gansxvavebuli eqsperimentebis safuZvelze warmoiqmna azri, rom
endoTeluri ujredebi ganapirobeben kunZulebis ganviTarebas (32, 37).
arsebobs kunZulebis ganviTarebis orsafexuriani modeli. pirveli
safexuri-endoTeluri ujredebi ganapirobeben pankreasis kunZulebis
ganviTarebas sadinrebis epiTelidan, Sedegad kunZulis ujredebi
ukavSirdebian sisxlZarRvebs. meore safexurze axali endoTeluri
ujredebi anviTareben kapilarul bades kunZuls gareT. es ori modeli
xsnis, Tu rogor arian dakavSirebuli Bβ-ujredebi sisxlZarღvovan
sistemasTan Tavis ganviTarebis adreul da Semdgom periodSi. swored am
ori sistemis urTierTkavSiriT xdeba pankreasis kunZulebis sekretoruli
funqciis uzrunvelyofa (33, 35, 36).
amgvarad pankreasis mikrovaskularuli qseli kargi modelia imis
gasagebad, Tu rogor xdeba endoTeluri ujredebis monawileoba organo
specifiur anTebiT procesebSi. bolo wlebis monacemebi pankreasis
86
mikrocirkulaciur wreSi mimdinare cvlilebebis PpaTo da morfogenezze
Saqriani diabetis dros sakmaod qaoturi da winaaRmdegobrivia.
zemoTqmulidan gamomdinare paTologebisaTvis da klinicistebisaTvis
sakmaod mniSvnelovania am cvlilebebis morfogenezis kompleqsuri
analizi da sistematizacia.
eqsperimentis dawyebidan 1 Tvis Semdeg, msubuqi mimdinareobis
aloqsanuri diabetis dros, umetesi kapilarebis sanaTuri gafarToebulia,
kapilaris kedeli warmodgenilia mxolod endoTeliT, romelic Seicavs
mravalricxovan fenestrebs. endoTeluri ujredebi qmnian kapilarebs
kunZulebs SigniT, raTa β-ujredebis mier gamoyofil sekrets SeeZlos
moxvedra sanaTurSi. zog adgilas endoTeli ganicdis distrofias da
deskvamacias. pankrasis kunZulebSi β-ujredebi uaxlovdeba 1 an 2
fenestრirebul kapilars. swored fenestrebi aris is Cqari gza, romliTac
insulini Sedis sisxlZarRvis sanaTurSi. SemaerTebeli qsovilis
raodenoba mcirea da xels ar uSlis sekretis gadaadgilebas. sxvanairad
gamoiyureba kapilaruli qselis venuri monakveTi. kerZod, is kapilarebi,
sadac ZiriTadad mimdinareobs nivTierebaTa cvla. es kapilarebi
amofenilia endoTeliocitebis Txeli SriT, romelTa Soris vlindeba
mravalricxovani fenestrebi. fenestrebs gaaCniaT damaxasiaTebeli
safarveli-diafragma (romelic xuravs fenestrebs). swored kapilarebis es
monakveTi xasiaTdeba maRali ganvladobiT, vinadian gaaCnia gansakuTrebuli
napraliseburi sivrceebi-kontaqtebi endoTeliocitebs Soris. aseTi
napralisebri kontaqtebis arsebobaze miuTiTeben sxva avtorebic Зуфаров,
(149).
paTologiuri procesis progresirebasTan erTad sxvadasva monakveTSi
gvxdeba araTanabarzomieri kapilarebi, sakmaod msxvili endoTeluri SriT.
kargad Cans endoTeliocitebis birTvebi. sainteresoa, rom am monakveTSi
cotaa endoTeliocitebs Soris fenestrebi aseT monakveTebSi kapilarebis
endoTelSi gazrdilia vakuolebis, vezikulebis, kaveolebis raodenoba.
amgvarad kaveolebi, veziko-vakuolebi, rogorc Cans is gzebia, romelic
xels uwyobs insulinis transendoTelur gadaadgilebas aloqsanuri
diabetis dros da warmoadgens adaptaciur kompensatoruli procesis
gamoxatulebas. erTeul endoTelur ujredebSi gvxvdeba cximis wveTebi.
87
sisxlZarRvebis kedeli mniSvnelovani metaboluri unaris mqone organoa,
romelsac aqvs unari iseTi komponentebis warmoqmnisa da sinTezirebisa,
rogoricaa kolageni, elastini, glikozaminglikanebi da amave dros
monawileoba miiRos plazmis sxvadasxva komponentebis katabolizmSi,
pirvel rigSi lipidebis, e.i. im nivTierebebis, romlebsac gaaCniaT unari
gaiaron ujredul barierSi da Semdeg SeaRwion intimaSi. eqserimentis
adreul vadebze sisxlZarRvis kedelSi lipidebis moxvedra SeiZleba iyos
araregulirebadi endocitozis Sedegad, an kidev endoTeliocitebs Soris
sivrcis gazrdis gamo. mogvianebiT ki ukve lipidebis transporti xdeba
dazianebuli, daSlili endoTeliocitebis kerebSi.
mZimed mimdinare aloqsanuri diabetis dros (glukoza sisxlSi 250
mg/%) perikapilaruli sivrce gazrdilia. arteriolebi warmodgenilia
erTis mxriv SeSupebuli endoTeluri ujredebiT, meores mxriv gamomSrali,
gauwylovanebeli endoTeliocitebiT. aseT ujredebSi organelebs gaaCniaT
gamomSrali, wvrili warmonaqmnebis Sexeduleba: endoTelis plazmolema
gafaSrebulia, membranebi ganSrevebuli. zogjer aRiniSneba plazmolizic.
xSir SemTxvevaSi membranis naglejebi moCans kapilaris sanaTurSic.
zogierTi kapilaris sanaTuri Sevsebulia TrombocitebiT da
eriTrocitebiT, rogorc Cans endoTelis dazianebas mohyveba
eriTrocitebis zedapiris Secvla (eriTrocitebi glikozirebuli
hemoglobiniT da Secvlili zedapiriT), maTi aglutinacia, stazi da
bolos Trombocitebis adgezia. zog monakveTebSi endoTeli ganicdis
proliferacias. gvxdeba axlad warmoqmnili sisxlZarRvebi. eleqtronul-
radioavtografiuli kvleviT aseT adgilebSi endoTeluri ujredebi
moiniSneba H3-Timidinze. imunohistoqimiuri kvleviT kunZulebis
kapilarebis endoTelis citoplazmaSi aRiniSneba CD 34-is eqspresia.
zogierTi avtorebis monacemebiT (36) insulinis deficiti aZlierebs
vaskularul endoTeluri zrdis faqtoris (WEGF-A) sekrecias da xels
uwyobs axali sisxlZarRvebis warmoqmnas. rigi avtorebis (36, 38, 175) azriT
insulin deficitur TagvebSi kapilarebi kunZulebSi metia da kunZulebic
didia. amgvaradACven vTliT, iq sadac insulinis deficitia WEGF-A-s
gamoyofa gaZlierebulia, es ki Tavis mxriv xels uwyobs axali kapilarebis
warmoqmnas. rogorc Cans WEGF-A faqtoris zrdis sapasuxod xdeba
88
endoTelis proliferaciis gaZliereba, endoTelis migracia da axali
sisxlZarRvebis warmoqmna pankreasis kunZulebSi, rac dasturdeba
imunohistoqimiuri da eleqtronul-radioavtografiuli kvleviT. amgvarad
endoTeluri ujredebi warmoqmnian axal kapilarebs kunZulis SigniT rac
aseve warmoadgens kompensatorul adaptaciuri procesis gamoxatulebas.
aloqsanuri diabetis dros morfologiuri cvlilebebis kompleqsi
viTardeba pankreasis kunZulebis mikrocirkulaციური wris yvela rgolSi,
ziandeba arteriolebi, kapilarebi, venulebi, sisxlZarRvTSorisi
anastomozebi. Cveni monacemebiT pirvel rigSi ziandeba arteriolebi.
paTologiuri cvlilebebi viTardeba wvrili sisxlZarRvebis yvela
struqturebSi, aRiniSneba sisxlZarRvis kedlis hialinozi, plazmuri
gaJRenTva, kedlis gasqeleba, intimis gafaSreba da adgil-adgil
endoTelis proliferacia, kunZulebis gazrda axladwarmoqmnili
kapilarebis xarjze.
amgvarad pankreasis kunZulebis endoTeluri ujredebi TamaSoben
mniSvnelovan rols I tipis diabetis dros. endoTeluri Sre warmoadgens
mniSvnelovan bariers sisxlis ujredebisaTvis. β-ujredebi da
mikrovaskularuli sistema erTad, kooperirebulad monawileoben
glukozis homeostazSi (33, 40).
aloqsanuri diabetis dros alteraciul cvlilebebs kunZulebis
endoTelSi (distrofia, deskvamacia), mosdevs anTebiTi da imunuri
ujredebis migracia transendoTelur sivrceSi da qsovilebSi, β-ujredebis
Semdgomi dazianebiT. paTologiuri procesis progresirebasTan erTad
aRiniSneba stromis SeSupeba, rac rogorc Cans ganpirobebulia
sisxlZarRvis kedlis gamtarobis gazrdiT. perikapilarul sivrceSi
vlindeba amorfuli wvrilmarcvlovani masa da mkveTrad osmiofiluri
erTeuli uxeSi kolagenuri boWkoebi. kapilarebis gaswvriv ganlagebuli
kolagenuri boWkoebi Rrmad Sedian kunZulebSi. perikapilarul sivrceSi
da kunZulebSi aRiniSneba infiltracia fibroblastebiT, limfocitebiT,
maკrofagebiT da plazmocitebiT. deendoTilizaciis zonaSi xSirad Cans
limfocitebis adhezia. endoTelis dazianebis adgilebSi limfocitebi
gvxvdeba monocitebTan da granulocitebTan erTad. zogjer qafisebri
ujredebis grZeli morCebi nawilobriv gars exvevian limfocitebs.
89
Eleqtronulი-radioavtografiiT bevri limfocitis birTvi moiniSneba H3-H
Timidinze, rac miuTiTebs am ujredebis proliferaciuli aqtivobis
zrdaze, amazeve miuTiTeben rigi avtorebi (35, 39, 149). mZimed mimdinare
paTologiuri procesis dros pankreasis kunZulebSi endokrinul ujredebs
Soris gamovlenili limfocitebi awveba da azianebs endokrinul
ujredebs. aseT limfocitebs gaaCniaT organelebiT Raribi citoplazma,
marcvlovani endopllazmuri badis StrixebiT da mitoqondriebis
umniSvnelo raodenoba.
eqsperimentis dawyebidan 1 Tvis Semdeg gansakuTrebiT bevria saSualo
zomis, varskvlaviseburi moyvanilobis fibroblastebi. eleqtronul-
radioavtografiuli meTodiT kvlevisas msubuqad mimdinare
eqsperimentuli diabetis dros fibroblastebi intensiurad moiniSneba H3-
-TimidiniT, zogierTi ki H3-uridiniT. mZimed mimdinare paTologiuri
procesis dros fibroblastebis citoplazma aqtiurad moiniSneba H3-
uridiniT rac miuTiTebs kolagenis intensiur produqciaze.
aloqsanis Seyvanidan 1 Tvis Semdeg aRniSneba Zlieri mononuklearuli
infiltracia, rogorc pankreasis kunZulebSi, ise maT garSemo. imunocitebi,
romlebic identificirebulia makrofagebad vlindeba pankreasis
kunZulebSi. makrofagebis didi nawili imyofeba fagocitozis stadiaSi da
inelebs daSlil β-ujredebs da lipidebs. Mmakrofagebis mniSvnelovan
rolze dazianebul kunZulebSi miuTiTeben mklevarebi (41). makrofagebis
citoplazmaSi aRiniSneba sxvadsxva zomis da simkvrivis lizosomebis
arseboba. am adgilebSi zogjer Cans kontaqti granularuli da
agranularuli endoplazmis badeebs Soris. makrofagebs gaaCniaT
sxvadasxva zomis wanazardebi, fsevdopoidebi. Eleqtroნul-
radioavtografiuli kvleviT makrofagebi aqtiurad moiniSneba rnm-is
winamorbediT. makrofagebi sisxlZarvis kedlis erT-erTi ZiriTadi
Semadgeneli nawilia, romlebic STanTqaven ra lipidebs,
transformirdebian qafisebr ujredebSi. rigi avtorebisa did yuradRebas
uTmobs monocitarul warmoSobis makrofagebs, vinaidan maT didi
raodenobiT gaaCniaT lipid-receptorebi anu “skvenjer” receptorebi
dabali simkvrivis lipidebis (LDL da VLDL) STanTqvisaTvis. receptorebiT
ganapirobebuli lipidebis StanTqვa mimarTulia homeostazis
90
SenarCunebisaken organizmSi. lipidebis arseboba sisxlSi astimulirebs
endoTelis hemataqsikuri faqtoris sekrecias, romelic xels uwyobs
monocitebis “gamoTesvas” sisxlidan, monocitebi Tavis mxriv amzadeben
endoTelis zedapirs monocitebis adheziisaTvis. swored am jaWviT aris
warmodgenili kompensatorul SeguebiTi reaqcia, romelic mimarTulia
“skvenjer” ujredebis mosazidad sisxlZarRvis kedelSi, romlebic
monawileoben lipidebis katabolizmSi.
eleqtronul-mikroskopuli da eleqtroნul-radioavtografiuli
kvlevis monacemebi amtkiceben, rom aloqsanuri diabetis dros gvxvdeba
gansxvavebuli simwifis da funqciuri aqtiვobis makrofagebi, limfocitebi,
plazmocitebi, fibroblastebi. am ujredebis funqciuri mdgomareoba da
raodenobrivi cvlilebebi dakavSirebulia aloqsanuri diabetis
simZimesTan. diabetis progresirebis Sesatyvisad aRiniSneba makrofagebis
raodenobis Semcireba; mwife H3-uridiniT moniSnuli fibroblastebis
raodenobis zrda, saTanadod kolagenis intensiuri warmoqmna, dnm-ze da
rnm-ze moniSnuli limfocitebis raodenobis zrda, rac rogorc Cans
ganpirobebulia adgilobrivi imunuri reaqciebis rRveviT.
Saqriani diabetis dros mniSvnelovan Teoriul da praqtikul interess
warmoadgens pankreasis kunZulebSi mimdinare β-ujredebis aRdgeniTi
procesebi. cnobilia, struqturul doneze insularuli ukmarisobis
kompensacia ZiriTadad ori gziT xorcieldeba:
1) hormonoproduqciis gaZlierebiT darCenili β-ujredebis funqciuri
aqtivobis gazrdis xarjze (19, 46, 47, 69) da
2) insularuli ujredebis proliferaciis gziT. Tumca ki, isic unda
iTqvas, rom diabetis dros β-ujredebis proliferacia mniSvnelovnad
CamorCeba maTi dazianebis xarisxs.
amJamad β-ujredebiს naklovanebis Sesavsebad ganixileba ori ZiriTadi
mimarTuleba:
1) β-ujredebis miReba in vivo da Semdgom transplantacia (66, 176).
2) β-ujredebis masis zrda (45, 58, 117, 177).
dResdReobiT, regeneraciuli medicinis mizania mravali daavadebis
samkurnalod, TerapiaSi gamoiyenos zrdasruli cxovelebis organoSi
arsebuli gardamavali tipis winamorbedebi da Rerovani ujredebi (70, 81,
91
93). axali kvlevebisa da hipoTezebis safuZvelze gamoyofilia β-ujredebis
aRdgenis gansxvavebuli gzebi:
1. arsebuli β-ujredebis proliferacia, replikacia da regeneracia (52, 53,
58, 60, 117, 178).
2. pankreasis sadinrebis epiTelis neogenezi da diferenciacia (63, 72, 74,
75, 79).
3. kunZulSida arsebuli ujredebis neogenezi (86-88).
4. pankreasis diferencirebuli ujredebis acinaruli, sadinrovani,
Rerovani ujredebis da pankreasis gareT arsebuli ujredebis
transdiferenciacia (77, 80, 83, 143, 150, 151, 154, 155, 179).
ujredebis generaciis sakiTxi winamorbedi ujredebidan sakmaod
sakamaToa da gansxvavebuli. didi xnis ganmavlobaSi mecnierebi
varaudobdnen, rom mxolod embrionul Rerovan ujredebs gaaCniaT
sxvadasxva tipis qsovilebis Seqmnis unari. embrionuli Rerovani ujredebis
diferenciacia β-ujredebSi mniSvnelovani midgomaa β-ujredebis wyaros
Sesaqmnelad. seriozuli Zalebi (6, 97, 109, 180) iyo mimarTuli embrionuli
Rerovani ujredebis diferenciaciiT mieRoT β-ujredebi. Tagvebis da
adamianis embrionis Rerovan ujredebTan muSaobam aCvena, rom embrionis
Rerovani ujredebidan β-ujredebis namdvili fenotipis miReba Znelia.
Tumca cxovelebis pankreasSi aRmoCenili iyo Rerovani winamorbedebi,
romlebic formirdebodnen β-ujredebSi stimulaciis Semdeg. winamorbedebi,
romlebic miRebuli iyo embrionidan warmoadgendnen namdvil Rerovan
ujredebs, maSin rodesac winamorbedebi zrdasruli virTagvebის
pankreasidan warmoadgendnen dediferencirebul ujredebs (91, 96, 98, 111).
rigi avtorebis azriT (55, 56, 74, 86, 90, 181, 182) cxovelebis pankreasSi
aRmoCenili winamorbedebi formirdebian β-ujredebSi sadinrebis
epiTelidan, acinaruli ujredebidan, kunZulebSi arsebuli sxva
endokrinuli ujredebidan da pankreasis gareT arsebuli sxva organoebis
ujredebidan (RviZli, nawlavis epiTeli, Zvlis tvini). interess moklebuli
ar aris is faqti, rom arapankreasis warmoSobis diferencirebulma
ujredebma SeiZleba awarmoon insulinis eqspresia pankreasis
transkripciuli faqtorebis gamoyenebis Semdgom (59, 69, 118, 119, 155, 183).
92
kvlevis safuZvelze aloqsanis Seyvanidan ukve 1 Tvis Semdeg
pankreasSi gamovlenili iyo kunZul gareT arsebuli gardamavali tipis
ujredebi. es ujredebi mdebareoben kunZulebTan axlos da amave dros
uSualo SexebaSi imyofebian acinozur da sadinrovan ujredebTan. naxevrad
Txel anaTalebze sazRvari acinarul da gardamavali tipis ujredebs
Soris mkveTradaa gamoxatuli. Catarebuli dakvirvebis safuZvelze
SeiZleba davuSvaT, rom aloqsanuri diabetis dros gardamavali tipis
ujredebi gvxdeba kunZul gareT, erT wilSi SeiZleba iyos 1-2 aseTi
ujredi. gardamavali tipis ujredebi vlindeba aloqsanuri diabetis
saSualo simZimis paTologiuri procesis dros da ar vlindeba mZime
formiს SemTxvevaSi. moyvanili faqti gvaZlevs safuZvels CavTvaloT es
ujredebi kompensaciur adaptaciuri procesis gamoxatulebad aloqsanuri
diabetis dros. swored amitom, kompensaciur adaptaciuri procesebis
Seswavlisas mniSvnelovan yuradRebas iqceven gardamavali tipis insulinis
granulebis Semcveli ujredebi da maTi lokalizacia.
pankreasis kunZulebis β-ujredebis generacia rogorc Cans xdeba
cxovelebis (Tagvi, virTagva, bocveri) pankreasSi arsebuli
winamorbedebisagan sxvadasxva stimulatorebis gamoyenebis Sedegad (67, 123,
125, 130, 132, 184, 185). kerZodEglukagonis msgavsi peptidebi, eqsedin-4,
gastrini, zrdis faqtorebi, aqtivin-A, betacelulini es is nivTierebebia,
romlebsac SeuZliaT β-ujredebis regeneraciis gaZliereba. momavalSi
swored, es iqneba axali mimarTuleba Saqriani diabetis mkurnalobis
sferoSi. cxovelebis pankreasSi myofi winamorbedebisagan pankreasis
ujredebis regeneracias Tagvebsa da virTagvebSi pankreasis sxvadasxva
dazianebis Semdeg aseve aRniSnaven rigi mklevarebisa (92, 186, 187).
β-ujredebis winamorbedebisa da Rerovani ujredebis stimulirebis
mizniT Cvens mier gamoyenebuli iyo biologiurad aqtiuri nivTiereba
plaferoni (amnioturi peptidi), preparati romelic miRebulia placentiს
amnioturi garsidan da xasiaTdeba imunomamodulirebeli, anTebis
sawinaaRmdego, antioqsidaturi, antivirusuli, antiapopturi,
hipoglikemiuri TvisebebiT. plaferonis zemoqmedebis Semdeg gansakuTrebul
yuradRebas ipyrobs gardamavali tipis erTmaneTisagan gansxvavebuli
ujredebi. am gardamavali tipis ujredebs pankresaSi aqvT gansxvavebuli
93
lokalizacia. es ujredebi imyofebian diferenciaciis da simwifis
sxvadasxva xarisxSi da mdgomareobSi. eleqtronul-mikroskopuli kvleviT
rig sadinrebis epiTelur ujredebSi gamovlenilia insulinis granulebi.
imunohistoqimiuri kvleviT sadinrebis epiTelur ujredebis citoplazmaSi
aRiniSneba CK 19-is Zlieri eqspresia, xolo kunZulebTan axlos arsebuli
sadinrebis erTeuli epiTeluri ujredebi iRebebian aseve anti insulinze.
rogorc Cans plaferoni aaqtiurebs sadinrebis ujredebis specifiur gens,
Zlierdeba am ujredebis proliferacia da Sesabamisad CK 19-is eqspresia.
Cven veTaxmebiT im avtorebis (76, 188, 189) azrs, romlebic β-ujredebis
winamorbedebad miiCneven pankreasis sadinrebis epiTelur ujredebs.
savaraudoa, rom moumwifebeli ujredebi sadinrovani fazis gavliT
gadadian diferencirebul β-ujredebSi. amgvarad, rogorc Cans plaferoni
aaqtiurebs β-ujredebis neogenezs sadinrovani ujredebidan. eleqtronul-
mikroskopuli kvlevis safuZvelze Cven mier gamovlenili iyo aseve
erTeuli acinaruli ujredebi, romlebic atareben rogorc acinarul, aseve
β-ujredebis niSan Tvisebebs. eleqtronogramaze zog ujredSi insulinis
granulebis raodenoba mcirea, zogierTSi ki bevri. gardamavali tipis
ujredebis polusi, romelic miqceuli iyo kunZulisaken Seicavs β-
ujredebisaTvis damaxasiaTebel granulebs, mkveTrad gamoxatuli garsiT,
mkvrivi guliT da asimetriuli naTeli arSiiT. citoplazmis es monakveTi
dabali eleqtronuli simkvrivisaa, vinaidan is Tavisufalia
organelebisagan. marcvlovani endoplazmuri badis cisternebs ar gaaCniaT
egzokrinuli ujredebisaTvis damaxasiaTebeli paraleluroba da
warmodgenili arian vezikulebiT da erTmaneTSi gadaxlarTuli mokle
cisternebiT, mcire raodenobiTaa ribosomebi. zogierT ujredSi
marcvlovani endoplazmuri badis retikulumi vlindeba CanarTis saxiT,
swored am ubnebSi didi raodenobiTaa β-insulocitebis granulebi.
mitoqondriebi wvrilia, Seicavs erTeul kristebs da naTel matriqs, rac
damaxasiaTebelia aseve β-ujredebisaTvis. citoplazmis sxva ubnebSi
SenarCunebulia marcvlovani endoplazmuri badis cisternebis
paraleluroba. amave dros mitoqondriebi msxvilia, momrgvalo-ovaluri
formis, eleqtronulad mkvrivi matriqsiT da mravalricxovani kristebiT,
aqve vlindeba zimogenuri granulebi e.i. yvelaferi is rac axasiaTebs
94
egzokrinul ujredebs. ეleqtronogramaze nawili ujredebisa
moTavsebulia acinusebTan axlos da Seicavs pankreasis kunZulebis β-
ujredebisaTvis damaxasiaTebel granulebs. Ees granulebi imyofebian an
perinuklearul zonaSi an kidev ujredis erT-erT polusTan. zog aseT
gardamavali tipis ujredSi insulinis granulebis gverdiT moTavsebulia
zimogenuri granulebi. am ujredebis birTvs aqvs gardamavali (Sualeduri)
agebuleba, kerZod qromatinis masaSi sWarbobs euqromatini.
imunohistoqimiuri kvleviT zogierTi aseTi ujredi iRebeba anti
insulinze. Cven aseve viziarebT im avtorebis (80, 143, 150). azrs, romlebic
miuTiTeben acino insularul transdiferenciaciis SesaZleblobaze.
pankreasis kunZulebSi iSviaTad vlindeba gardamavali tipis
ujredebi, romelic erTdroulad Seicavdnen Aα-ujredisaTvis
damaxasiaTebel glukagonis da β-ujredebisaTvis damaxasiaTebel erTeul
insulinis granulebs.
pankreasis kunZulebis β-ujredebis winamorbedebis warmoSobaze da
bunebaze arsebuli kvlevebi urTierTsawinaaRmdegoa, problematuria da
dResac warmoadgens diskusiis sagans. mTeli rigi avtorebis (73, 86, 95, 151,
190). mierKkargad aris aRwerili da dokumentirebuli β-ujredebis
neogenezi sadinrebis epiTelidan, acino-insularul transdiferenciaciaze
miuTiTeben rigi mkvlevarebi (151, 154, 191), zogi avtori (87, 88) β-ujredebis
potenciur wyarod miiCnevs TviT kunZulebSi arsebul endokrinul
ujredebs. pankreasis kunZulebis endokrinul ujredebs Soris glukagonis
warmomqmneli ujredebi aris pirveli endokrinuli ujredebi, romlebic
ganicdian diferenciacias da transformacias insulinis warmomqmnel
ujredebSi (86). zogierTi mkvlevaris (52, 53, 58, 117) azriT β-ujredebis
warmoqmna xdeba kunZulebSi fakultaturi ujredebis proliferaciiT da
replikaciiT. epiTelur mezenqimur gardaqmnaze weren rigi avtorebisa (95,
157, 179, 192).
amgvarad Cveni monacemebi emTxveva im mkvlevarebis (47, 81, 156) azrs,
romlebic miuTiTeben gardamavali tipis β-ujredebis winamorbedebis
arsebobaze pankreasSi. es ujredebi imyofebian funqciurad mosvenebul
mdgomareobaSi rogorc paTologiis, ise fiziologiis pirobebSi da am
gardamavali tipis ujredebidan Sesaძlebelia endokrinuli ujredebis
95
warmoqmna stimulaciis Semdeg, Tumca ki zogierTi avtori (70, 91, 93) β-
ujredebis winamorbedebad miiCnevs damoukidebel Rerovan ujredebs,
romlis funqcia jer kidev gaurkvevelia.
Catarebuli dakvirvebis safuZvelze SeiZleba davuSvaT, rom
aloqsanuri diabetis dros β-ujredebis niSan-Tvisebebis mqone gardamavali
tipis ujredebi gvxdeba rogorc kunZul gareT aseve kunZulebSic.
pankreasis sadinrovan, acinarul da kunZulebis rig endokrinul ujredebs
da Rerovan ujredebs aqvT unari neogenezis, replikaciis, diferenciaciis,
transdiferenciaciis gziT gardaiqmnan β-ujredebad rigi stimulatorebis,
Cvens SemTxvevaSi plaferoniT zemoqmedebis Semdeg. swored
mastimulirebeli faqtorebis gamoyeneba zrdasruli cxovelebis pankreasSi
arsebuli winamorbedebis mimarT, SeiZleba gaxdes β-ujredebis masis zrdis
mizezi.
Cveni kvlevis safuZvelze plaferoniT zemoqmedebis Semdeg
gansakuTrebul yuradRebas ipyrobs izolirebulad myofi β-ujredebi. es
ujredebi ar arian organizebuli kunZulebSi. Cvens mier eqstra
insularul komponentad miRebuli iyo is ujredebi, romlebic Seicavs
insulinis mwife granulebs da romlebSiac kargad vlindeba birTvi. A
ujredebis simwifis da funqciuri aqtivobis dasadgenad Catarebulia
eleqtronul-morfometruli kvleva. miRebuli monacemebi damuSavebulia
statistikurad. daTvlilia insulinis granulebis raodenoba, naTeli da
muqi insulinis granulebis raodenoba da am granulebis procentuli
Sesabamoba, insulinis granulebis diametri da maT mier dakavebuli
sivrce. miRebul monacemebs vadarebdiT aloqsanis da sakontrolo jgufis
virTagvebis pankreasis kunZulebis β-ujredebis insulinis granulebs.
Eleqtronul-morfometrulma kvlevam gviCvena arsebuli sxvaoba daTvlil
parametrebs Soris. miRebuli monacemebis safuZvelze dadginda, rom
izolirebul β-ujredebSi aloqsanur da sakontrolo jgufTan SedarebiT
mniSvnelovnad momatebulia naTeli insulinis granulebis raodenoba. Cven
vvaraudobT, rom naTeli granulebis mateba miuTiTebs am β-ujredebis
unarze awarmoon insulinis swrafi sekrecia gansxvavebiT muqi
granulebisagan, romelTa siWarbe miuTiTebs ZiriTadad sekretis
dagrovebaze. Cven veTanxmebiT im avtorebis azrs (9, 20, 169, 193), romlebic
96
naTeli insulinis granulebis matebas β-ujredebSi ukavSireben insulinis
swraf sekrecias.
აmgvarad Cveni kvlevis safuZvelze SeiZleba vivaraudoT, romBpankreass
gaaCnia ujreduli plastiuroba da aqvs unari dasabami misces
multipotentur progenitorebs, rasac aseve aRniSnaven rigi mkvlevarebisa
(74, 135, 137, 176, 194). Cveni Sedegebi TvalnaTliv miuTiTeben, rom pankreasis
sadinrovan, acinarul, endokrinul da Rerovan ujredebs aqvT poteciali
diferencirdnen pankreasis β-ujredebSi. swored es aris pirveli nabiji β-
ujredebis regeneraciisa in vitro da warmoadgens diabetis axali Terapiuli
mkurnalobis safuZvels. plaferoni xels uwyobs pankreasSi arsebuli
winamorbedi ujredebis β-ujredebSi neogenezis, diferenciaciis,
transdiferenciaciis process. savaraudoa, rom plaferoni virTagvebis
pankreasSi astimulirebs β-ujredebis generacias winamorbedi da Rerovani
ujredebidan.
Cveni monacemebis safuZvelze SeiZleba davaskvnaT, rom arsebuli
mastimulirebeli faqtoris gamoyeneba amcirebs hiperglikemias, magram ar
dahyavs glukoza miRebul normamde. vaCvenebT ra β-ujredebis
winamorbedebis arasrulfasovnebas gamoimuSaon insulinis sakmarisi
raodenoba vvaraudobT, rom arsebuli midgomis SezRuduli
SesaZleblobebi SeiZleba gamowveuli iyos Semdegi mizezebiT:
1) diferencirebuli ujredebis arasruli dediferenciacia winamorbed
ujredebis mgomareobamde;
2) dediferencirebuli winamorbedebis arasakmarisi rediferenciacia β-
ujredebSi;
3) insulinis mwarmoebul ujredebis SezRuduli unari, awarmoon
proliferacia da momwifdnen glukozaze moreagire ujredebis donemde. P
plaferoni aseve garkveul gavlenas axdens mikrovaskularul
kalapotSi mimdinare cvlilrbebze. plaferoniT zemoqmedebis Semdeg
virTagvebis pankreasis kunZulebis sinusoidebSi endoTeli Txelia,
fenestrirebuli. Cveni varaudiT plaferoni aZlierebs antioqsidaciur da
antiinflamaciur procesebs, aregulirebs oqsidaciur metabolizms
vaskularul sistemaSi, aRadgens redoqs damokidebul nitrit oqsidebis
aqtivobas da amcirebs sinusuri kapilarebis endoTelis dazianebis
97
xarisxs. zog monakveTebSi endoTeli ganicdis Zlier proliferacias.
Cndeba axlad warmoqmnili sisxlZarRvebi. eleqtronul-
radioavtografiuli kvleviT am monakveTebSi endoTeli aqtiurad
moiniSneba H3-TimidiniT, xolo imunohistoqimiuri kvleviT kunZulebis
kapilarebis endoTelis citoplazmaSi aRiniSneba CD 34-is Zlieri eqspresia,
rac miuTiTebs angiogenezis procesis mkveTr zrdaze. CD 34-is mimarT
pozitiuri ujredebi gabneulia mTel pankreasSi. rac Tavis mxriv mianiSnebs
Zvlis tvinis warmoSobis Rerovani ujredebis mobilizaciis aqtivaciaze.
plaferonis zemoqmedebis Semdeg kunZulebis perikapilarul sivrceSi
aRiniSneba fibrozuli CanarTebis Semcireba. Cveni varaudiT es gamowveulia
makrofagebis aqtivaciiT. rogorc Cans plaferonis zemoqmedebiT, izrdeba
lizosomebis enzimebiT eqskreti da Sesabamisad Zlierdeba boWkoebis
lizisi.
amgvarad aSkaraa, rom ZiriTad moments, romelic ganapirobebs
daavadebis manifestacias, misi mimdinareოbis simZimes aris pankreasis
kunZulebis β-ujredebis dazianebis xarisxi. kvlevis Sedegebis analizi
saSualebas gvaZlevs davadginoT, rom aloqsanuri diabetis dros
pankreasis kunZulebSi aRiniSneba ujredebis Zlieri destruqcia, nekrozi
da apoptozi, romlis paTogenur safuZvels warmoadgens cvlilebebi
mikrocirkulaciur sistemaSi (endoTelis distrofia, deskvamacia,
Camofcqvna da sxva) endoTeluri Sris barieris moSlas, mosdevs anTebiTi
da imunuri ujredebis (makrofagebis, limfocitebis, plazmocitebis)
migracia perikapilarul sivrceSi da kunZulebSi. aqtiuri, mwife
fibrolastebis gaCena, rac Tavis mxriv aZlierebs ujredebis dazianebis
xarisxs. amgvarad aloqsanuri diabetis dros viTardeba
urTierTganpirobebuli progresirebadi cvlilebebi mikrocirkulaciur
wreSi da β-ujredebSi. am morfologiuri cvlilebebis gamoxatuleba
pirdapir kavSirSia paTologiuri procesis simZimesTan.
aloqsanuri diabetis dawyebidan 1 Tvis da 10 dRiani plaferonis
kursis Semdeg virTagvebis sisxlSi glukozis Semcveloba mcirdeba 50-60
mg%iT. virTagvebis pankreasis kunZulebSi mniSvnelovani cvlilebebi ar
aRiniSneba. plaferoniT zemoqmedebis Semdeg virTagvebis pankreasis
kunZulebSi nekrobiozuli cvlilebebis paralelurad gvxdeba
98
hipertrofuli kunZulebi erTeuli ujredebiT, romlebSiac aRiniSneba
mitozebi. vizualurad Semcirebulia apoptozuri ujredebiს raodenoba.
plaferoni, rogorc Cans icavs pankreasis qsovils dazianebisagan, romelic
gamowveulia aloqsaniT. plaferoni awarmoebs pro-inflamatoruli
citokinebis sinTezis da Tavisufali radikalebis reproduqciis
inhibirebas. savaraudoa, rom plaferoni gvevlineba β-ujredebis damcvelad,
awarmoebs ra mitoqondriuli potencialis aRdgenas, aZlierebs β-ujredebis
proliferacias, misi mitogenuri aqtivobis gazrdiT (165). aloqsaniT
dazianebul virTagvebis pankreasSi plaferoni xels uwyobs β-ujredebis
generacias winamorbedi da Rerovani ujredebidan, Tumca ki ver axerxebs
insulinis deficitis srul kompensacias organizmSi. Kplaferoni Tavisi
antioqsidaciuri da antiinflamaciuri TvisebebiT axdens metabolizmis
stabilizacias mikrocirkulaciur sistemaSi da amcirebs endoTelis
dazianebis xarisxs sinusoiduri tipis kapilarebSi. aloqsaniT dazianebul
virTagvebis pankreasSi plaferoni xels uwyobs β-ujredebis generacias
winamorbedi da Rerovani ujredebidan, Tumca ki ver axerxebs insulinis
deficitis srul kompensacias organizmSi. K
Ealoqsanuri diabetis dros mamr virTagvebis sisxlSi aRiniSneba
adaptaciuri hormonebis kortikosteronis da somatotropinis plazmuri
koncentraciis zrda, aromatizaciis procesebis aqtivacia, testosteronis
koncentraciis Semcireba, gamowveuli misi aromatizaciis aqtivaciiT,
estradiolis raodenobis momateba, dnm-isa da rnm-is sinTezis Semcireba.
rogorc Cans, aloqsanuri diabetis dros mamr virTagvebSi xdeba
metaboluri da hormonuli TviTregulaciis moSla, romelic vlindeba
metaboluri stresis saxiT.
sinTezuri radioinertuli androgen- meTiltrieნolonis yoveldRiuri
or kviriani kursis Semdgom mamr virTagvebis sisxlSi, aloqsanur diabetis
virTagvebis sisxlSi arsebul monacemebTan SedarebiT, aRiniSneba
glukozis koncentraciis Semcireba, rac rogorc Cans ganpirobebulia
qsovilebis insulinisadmi mgrZnobelobis gazrdiT. kortikosteronisa da
somatotropinis koncentraciis Semcireba, aromatizaciis procesebis
Seneleba, estradiolis da testosteronis koncentraciis zrda da
miaxloeba normasTan, dnm-isa da rnm-is sinTezis aqtivacia, pankreasis
99
kunZulebSi – ujredebis proliferaciis aqtivacia. testosteronis
plazmuri koncentaciis miaxloeba normasTan xels uwyobs pankreasSi
aqtiuri androgen receptorebis gajirjvebas testosteroniT, rasac
mosdevs Tavisufali receptorebis Semcvelobis Semcireba. testosteronis
citoproteqtuli efeqti, rogorc Cans dakavSirebulia antioqsidaciuri
enzimebis induqciasTan β-ujredebSi. literaturuli monacemebiT (10, 160)
sasqeso steroidebis moqmedebis meqanizmi mdgomareobs maT
urTierTqmedebaSi cilovan receptorebTan, steroid receptoruli
kompleqsis translokaciaSi birTvSi da maT urTierTqmedebaSi birTvis
qromatinis aqceptorebTan. Sedegad xdeba birTvis qromatinis struqturis
Secvla, transkripciis da ujreduli cilebis sinTezis Secvla, romlebic
Tavis mxriv aCqareben kompensatorul procesebs. Aamgvarad Cveni varaudiT
androgenebi iReben monawileobas organizmSi mimdinare metabolur da
kompensatorul procesebSi. androgenuli regulaciis efeqturoba
ganisazRvreba rogorc hormonis koncentraciis SemcvelobiT, aseve
ujredebSi androgenuli receptorebis doniT. miRebuli monacemebi emTxveva
rigi mkvlevarebis azrs (161, 162) androgenebis regulatorul moqmedebaze
sqesiT diferencirebul cxovelebSi mimdinare adaptaciur procesebze.
kvlevis safuZvelze pankreasSi gamovlenili parenqimul-stromuli
elementebis urTierTdakavSirebuli cvlilebebi safuZvels gvaZlevs
vimsjeloT ara marto paTologiur Zvrebze, aramed im kompensaciur-
adaptaciur procesebzec, romelic viTardeba virTagvebis pankreasSi
aloqsanuri diabetis dros, plaferoniTa da sinTezuri radioinertuli
androgen-meTiltrieნolonis zemoqmedebis Semdeg.
100
დასკვნა
1. Seswavlilia β-ujredebis morfo-funqciuri suraTi aloqsanuri
diabetis ganviTarebis da Camoyalibebis procesSi. dadgenilia, rom es
cvlilebebi aris Saqriani diabetis klinikuri gamovlinebis ZiriTadi
morfologiuri maCvenebeli da asaxavs aloqsanuri diabetis rogorc
simZimes, ise stadias. es morfologiuri maCvenebeli damokidebulia
glukozis Semcvelobaze sisxlSi.
2. gamovlenilia urTierTdamokidebuleba erTis mxriv B β-insulinis
warmomqmnel ujredebs da meores mxriv glukagonis da somatostatinis α
da δ ujredebs Soris. dadgenilia, rom aloqsanuri diabetis dros,
pankreasis endokrinuli nawili naxSirwylebis cvlis moSlaze
kompleqsurad pasuxobs misi yvela komponentebis met-naklebi
monawileobiT.
3. aloqsanuri diabetis dros pankreasSi gamovlenilia multipotenturi
progenitorebi. es ujredebi moTavsebulia sadinrebTan da acinusebTan
axlos da atareben, rogorc pankreasis acinaruli, sadinrebis epiTelis
da kunZulSida endokrinuli ujredebis, aseve Bβ-ujredebis niSan
Tvisebebs. kvlevebiT dadgenilia, rom eqsperimentuli diabetis
pirobebSi es gardamavali tipis ujredebi imyofebian mosvenebul
mdgomareobaSi, razedac miuTiTebs maTSi arsebuli sekretoruli
granulebis simwifis xarisxi.
4. aloqsanuri diabetis dros virTagvebis pankreasSi aRiniSneba
urTierTganpirobebuli, progresirebadi cvlilebebi mikrocirkulaciur
wreSi (enoTelis distrofia, deskvamacia, fenestrebis raodenobis
101
Semcireba) da sxvadasxva xarisxis dazianebebi pankreasis kunZulebis β-
ujredebSi (distrofia, nekrozi), am morfologiuri cvlilebebis
gamoxatuleba pirdapir kavSirSia aloqsanuri diabetis simZimesTan.
5. pankreasis kunZulebis SemaerTebel qsovilSi gamovlenili cvlilebebi
(kunZulebSi uxeSi fibrozuli boWkoebis gaCena, kunZulebis struqturis
rRveva) histio-limfocitaruli infiltracia perikapilarul sivrceSi
da kunZulebSi zrdis β-ujredebis dazianebis xarisxs paTologiuri
procesis simZimis proporciulad.
6. aloqsanuri diabetis dros pankreasis kunZulebSi Tanmimdevrulad
ganviTarebuli cvlilebebi uSualo kavSirSia paTologiuri procesis
simZimesTan, es ki saSualebas gvaZlevs mkveTrad ganvsazRvroT β-
ujredebis dazianebis xarisxi, gamovyoT Seqcevadi cvlilebebi
Seuqcevadisagan, rasac TeoriulTan erTad aqvs didi praqtikuli
mniSvneloba. miRebuli monacemebis safuZvelze SeiZleba davaskvnaT, rom
aloqsanuri diabetis dros qsovilovan doneze moqmedebs meqanizmebi,
romlebic avtomaturad uzrunvelyofen parenqimisa da stromis
urTierTregulacias.
7. plaferoniT zemoqmedebis Semdeg klebulobs glukozis koncentracia
virTagvebis sisxlSi. adgili aqvs sklerozuli procesis Seqcevadobas,
kerZod, fibrozuli Sreebis rezorbacias (aseT ubnebSi Warbadaa
makrofagebi). miRebuli monacemebis safuZvelze SeiZleba davaskvnaT, rom
plaferoni aaqtiurebs makrofagebs. makrofagebis mier gamoyofili
lizosomuri fermentebiT xdeba kolagenuri boWkoebis lizisi, rac
Tavis mxriv xels uwyobs sekretis gadaadgilebas sisxlZarRvis
sanaTurSi da warmoadgens kompensaciur adaptaciuri procesesis
gamovlinebas.
102
8. plaferoniT zemoqmedebis Semdeg pankreasis kunZulebSi da kunZul
gareT vlindeba gardamavali tipis ujredebi mkveTrad gamoxatuli β-
ujredebis niSanTvisebebiT. am gardamavali tipis ujredebs aqvT maRali
sekretoruli aqtivoba da maTSi ar aRiniSneba destruqciuli
cvlilebebi. miRebuli Sedegebis safuZvelze SeiZleba davaskvnaT, rom
gardamavali tipis ujredebs aqvT potencia neogenezis, diferenciaciis
da transdiferenciaciis gziT diferencirdnen pankreasis β-ujredebSi
stimulaciis Semdeg.
9. virTagvebis aloqsan-plaferonis jgufSi gamovlenilia izolirebuli β-
ujredebi. es ujredebi ar arian organizebuli kunZulebSi. am β-
ujredebis mier gamoyofili sekreti aumjobesebs, magram ar dahyavs
normamde glukozis raodenoba sisxlSi. plaferoni amcirebs
hiperglikemias, Tumca ki ver axerxebs insulinis deficitis
kompensacias organizmSi.
10. amgvarad pankreasis sadinrebis epiTelur, acinarul da rig endokrinul
da Rerovan ujredebs gaaCniaT ujreduli plastiuroba da SeuZliaT
diferencireba pankreasis kunZulebis β-ujredebSi plaferonis
zemoqmedebiT.
11. androgenebi iReben monawileobas organizmSi mimdinare metabolur da
kompensatorul procesebSi. androgenuli regulaciis efeqturoba
ganisazRvreba rogorc hormonis koncentraciis SemcvelobiT, aseve
ujredebSi androgenuli receptorebis doniT.
103
12. arsebuli monacemebi saSualebas mogvcems momavalSi pankreasis
endokrinuli nawilis potenciuri saSualebebis gamoyenebiT
gamovimuSaoT mkurnalobis axali alternatiuli meTodebi.
104
SUMMURY
The ability of dysfunctional β-cell lesions to regulate blood glucose levels can be normalized in by
increasing the mass of existing β-cells in the pancreas. This approach can be achieved by the
regeneration, proliferation, and replication of pre-existing β-cells, as well as by the neogenesis of β-
cells from precursor, stem cells or by trans-differentiation from other differentiated cells.
In the present study we induced alloxan diabetes in experimental animal model and studied the
influence of Plaferon LB (amniotic derived peptide) and radio-inert synthetic androgen
methyltrienolon on renewal processes of the pancreas. Histological, electrono-microscopical,
immunohistocemical, electron-morphometrical and radio-immune methods in the pancreases of rats
with alloxan-induced diabetes were studied. From a total of 120 Wistar laboratory rats, 30 received
an alloxan injection to induce diabetes and were treated one month later with Plaferon LB (0.25
mg/g) (Alloxan/Plaferon LB-treated group). Thirty male rats with Alloxan diabetes were treated one
month later with radio-inert synthetic androgen methyltrienolon and rats with Alloxan diabetes
received an alloxan injection but no subsequent treatments (Alloxan-treated group), and a control
group of 30 rats (Control group). The blood glucose level was used as a marker for Alloxan-induced
diabetes. Pieces of pancreas were sampled and tissue morphological analysis was undertaken after
cessation of experiment.
In Alloxan-treated group, changes such as dystrophy and necrosis were apparent not only in the β-
cells but also in the vascular system of the pancreatic islets. During the development of alloxan-
induced diabetes in our study, the endothelium underwent alterations (dystrophy and desquamation
of the endothelium) followed by the transendothelial migration of immune and inflammatory cells
(macrophages, lymphocytes, plasmocytes,) into the pericapillary space and the endocrine tissues,
with consequent progressive injury of the β-cells. Alloxan/Plaferon LB-treated group presented
endothelial layers that appeared thin and well-fenestrated, having pericapillary spaces without
fibrous inclusions.
Based on our findings, we suggest that Plaferon LB exerts antioxidant and anti-inflammatory
effects, stabilizing oxidative metabolism in the vascular system and decreasing the intensity of
injury in the endothelium of the sinusoidal capillaries. In Alloxan/Plaferon LB-treated group, extra
islet transitional cells were observed containing granules with varying degrees of maturation and
105
exhibiting features specific for insulin-secreting β-cells. Immunohistochemical analyses showed
that CD 34 positive cells were located within islets and scattered throughout pancreas. Endothelial
cells of islet sinusoidal capillaries strongly expressed by CD 34. According to this finding we
hypothesized that Plaferon LB activates processes of endothelial proliferation and initiates
formation of new capillaries. Subpopulations of cells adjacent to the ductal epithelium contained
CD 34 positive precursor cells and perhaps giving rise to β-cells. Evidently in diabetic rats pancreas
Plaferon LB activate angiogenic processes and mobilization of bone marrow- derived cells. In
Alloxan/Plaferon LB-treated group immunohistochemical analysis also revealed strong expression
of Cytokeratin 19 (CK19) in the duct cells nearby pancreas islets, we support the idea that β-cell
progenitors go through a ductal phase from an immature to an adult β-cell. Plaferon LB as it seems
activated neogenesis of β-cells from duct cells. Electron-microscopic findings suggest that β-cell
precursors are not restricted to only pancreatic ducts, and generate also through acino-insular trans-
differentiation. In the present study single acinar cells including insulin granules were manifested in
the ducts near the islets. We agree with opinion of some authors specifying on a possibility of
acino-insular transdifferentiation from exocrine tissue. Electrono-morphometric analysis of insulin
granules in the extra-islet isolated β-cells showed increased proportion of light granules which is
associated with increased insulin secretion. Present results suggest that Plaferon LB:
Promotes a decrease in the blood glucose level;
Helps to stabilize oxidative metabolism in the vascular system and to decrease the intensity
of endotheliocyte injury;
Encourages the maturation and differentiation of transitional precursor cells;
Induces the renewal of β-cells in the pancreas of rats with alloxan-induced diabetes.
Treatment with Plaferon LB appears to enable the damaged pancreas to generate new β-cells
The two-week everyday application of radio-inert synthetic androgen methyltrienolon caused in
male rats with Alloxan diabetes sharp increase of testosterone concentration in blood serum (92 %
from 52 % initial) and was accompanied with decrease in glucose concentration (43 % from initial)
due to the increased sensitivity of tissues to insulin. Testosterone active androgen receptors in the
pancreas islet, reducing the content of free receptors to 121 % with control indicators equal to 210
%. Testosterone has an inhibitory effect on the catabolic action of glucocorticoids and improves
state of β-cells which was confirmed by radiometry showing an increase of DNA and RNA in these
106
animals compared with the control of DNA synthesis by 16 % and 12 % RNA. These findings are
consistent with the opinion of some authors about regulatory effects of androgens on sex-
differentiated and adaptive responses of the male body. Our results suggest that in Alloxan/Plaferon
LB-treated group extra- and intra-islet transitional cells exist in a resting condition and can
differentiate into β-cells. Based on the properties we observed in these transitional cells, we
conclude that subsets of these cells were derived from acinar, ductal, and endocrine cells, or even
from non-differentiated stem cell. Presumably, Plaferon LB stimulates the maturation and
differentiation of β-cell precursors and participates in the renewal process of β-cells in the diabetic
rat’s pancreas. When radio-inert synthetic androgen methyltrienolon caused in male rats with
Alloxan diabetes stimulate proliferation of pancreas islets β-cells. However the effect of Plaferon
LB and radio-inert synthetic androgen methyltrienolon are not sufficient to compensate for insulin
deficiency.
107
გამოქვეყნებული შრომების სია
1. Extra-islet intermediate cells of pancreas and effect of Plaferon in Alloxan induced diabetes
mellitus. Bulletin of the Georgian National Academy of Sciences 2009, 3, 3:169-172.
Latsabidze I. Machavariani T. Gachechiladze I. Gvamichava T. Kavtiashvili K.
2. virTagvas pankreasis kunZulebSi mimdinare morfologiuri
cvlilebebi aloqsanuri diabetis dros da plaferoniT
zemoqmedebisSemdeg. eqsperimentuli da klinikuri medicina 2010; 3 (58);
12-15. i.lacabiZe.
3. Beta-cells of Rats Pancreas and their Supposed Precursors during Alloxan Diabetes and
after the Action of Plaferon LB. Georgian Medical News, 2011, 9,198:40-45.
Latsabidze I. Machavariani T. Gachechiladze I. Gvamichava T. Kavtiashvili K.
4. virTgvebis pankreasis kunZulebis mikrocirkulaciur wreSi
ganviTarebuli struqturuli cvlilebebi aloqsanuri diabetis
dros. eqsperimentuli da klinikuri medicina 2014; 1, 34-36. i.lacabiZe,
T.maWavariani, i.gaCeCilaZe, T.RvamiCava.
5. virTagvebis pankreasSi ganviTarebuli ultrastruqturuli
cvlilebebi aloqsanuri diabetis dros. eqsperimentuli da
klinikuri medicina 2014; 5, 60-62. i.lacabiZe, T. maWavariani,
T.RvamiCava, i.gaCeCilaZe.
6. Корекция гормонально-метаболических нарушений у самцов крыс с
развивающимся экспериментальным диабетом. Бюлетень Экспериментальной
Биологии и Медицины. Изд. Росс. Акад. Мед. Наук 2015 Том 159, № 1 ЯНВАРЬ.
Н.А. Дидебулидзе, М.Ш. Какабадзе Н.Г. Гордадзе И.Н. Лацабидзе М.Э.
КордзаяИ.Т. Сихарулидзе.
108
ლიტერატურა
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