CAJ | 학술논문

目的探讨新生猪Sertoli细胞(NPSCs)与大鼠胰岛细胞联合移植对延长大鼠同种异体胰岛移植物存活时间的作用及其主要的机制.方法将糖尿病Wistar大鼠随机分为3组.(1)单纯移植组(n=6):单纯移植1500个胰岛当量(IEQ)的SD大鼠胰岛细胞至糖尿病大鼠的左肾包膜下;(2)分侧移植组(n=4):将1500个IEQ的SD大鼠胰岛细胞移植到糖尿病大鼠的左肾包膜下,同时将1×10~7个NPSCs移植到糖尿病大鼠的右肾包膜下;(3)混合移植组(n=6):将1500个IEQ的SD大鼠胰岛细胞和1×10~7个NPSCs混合移植到糖尿病大鼠的左肾包膜下.移植后每天监测各组的血糖水平,以了解移植物的存活时间;移植后发生排斥反应时获取移植物标本,行HE和免疫组织化学染色,观察移植物中CD3~+T淋巴细胞浸润情况及细胞凋亡调控基因(Bcl-2)和血红素氧合酶1(HO-1)基因的表达水平.结果单纯移植组、分侧移植组和混合移植组胰岛移植物存活时间分别为(5.7±1.0)d、(5.3±0.5)d和(16.3±1.4)d,混合移植组存活时间较其他两组显著延长(P<0.05).单纯移植组移植区可见大量淋巴细胞浸润,主要为CD3+T淋巴细胞;混合移植组移植区Bcl-2基因呈高表达;各组移植区HO-1基因均有表达,差异不明显.结论 NPSCs与大鼠胰岛细胞联合移植可以延长大鼠同种异体胰岛移植物的存活时间,其机制可能与NPSCs抑制移植物淋巴细胞浸润、促进Bcl-2基因高表达的局部免疫调节作用有关.
목적 탐토신생저Sertoli세포(NPSCs)여대서이도세포연합이식대연장대서동충이체이도이식물존활시간적작용급기주요적궤제.방법 장당뇨병Wistar대서수궤분위3조.(1)단순이식조(n=6):단순이식1500개이도당량(IEQ)적SD대서이도세포지당뇨병대서적좌신포막하;(2)분측이식조(n=4):장1500개IEQ적SD대서이도세포이식도당뇨병대서적좌신포막하,동시장1×10~7개NPSCs이식도당뇨병대서적우신포막하;(3)혼합이식조(n=6):장1500개IEQ적SD대서이도세포화1×10~7개NPSCs혼합이식도당뇨병대서적좌신포막하.이식후매천감측각조적혈당수평,이료해이식물적존활시간;이식후발생배척반응시획취이식물표본,행HE화면역조직화학염색,관찰이식물중CD3~+T림파세포침윤정황급세포조망조공기인(Bcl-2)화혈홍소양합매1(HO-1)기인적표체수평.결과 단순이식조、분측이식조화혼합이식조이도이식물존활시간분별위(5.7±1.0)d、(5.3±0.5)d화(16.3±1.4)d,혼합이식조존활시간교기타량조현저연장(P<0.05).단순이식조이식구가견대량림파세포침윤,주요위CD3+T림파세포;혼합이식조이식구Bcl-2기인정고표체;각조이식구HO-1기인균유표체,차이불명현.결론 NPSCs여대서이도세포연합이식가이연장대서동충이체이도이식물적존활시간,기궤제가능여NPSCs억제이식물림파세포침윤、촉진Bcl-2기인고표체적국부면역조절작용유관.
Objective To investigate whether cotransplant with xenogenetic neonatal porcine Sertoli cells (NPSCs) could prolong rat islet allograft survival and its mechanisms.Methods 1500 islets equivalent quantity (IEQ) and 1×10~7 NPSCs were implanted under renal capsule of diabetic Wistar rats.Islets implanted alone were used as control group (n=6);islets co-transplanted with NPSCs under left renal capsule of recipients served as experimental group (n=6);meanwhile,islets and NPSCs implanted into the different sides of kidneys were used as another control grouP(n=4).Blood glucose level was measured everyday.The graft-bearing kidneys at the time of rejection were Results Co-transplantation with NPSCs to the same site significantly prolonged islet allograft survival (mean survive time,16.3±1.4 days vs.5.7±1.0 days in islet transplant alone control group,P<0.05).In contrast,transplantation with NPSCs and islets separately did not prolong the islet allograft survival (5.3±0.5 days).HE staining showed plenty of local infiltrated lymphocytes in the transplanted site of the eontrol group.which were demonstrated as mainly CD3+ T cells by immunopathology.The local expression of Bcl-2 was markedly elevated in co-transplantation group as compared with the other 2 groups,while there were no significant differences in the HO-1 expression among these groups.Conclusion Co-transplantation with xenogenic NPSCs can significantly prolong islet allograft survival in rats.The immunoprotective mechanism may be associateel with the inhibition of lymphocyte infiltration and the enhancement of the local expression of protective gene Bcl-2.