新生猪Sertoli细胞与大鼠胰岛细胞联合移植延长大鼠移植胰岛的存活时间  

Prolongation of islet allograft survival in rats by cotransplantion with xenogenetic neonatal porcine Sertoli cells

作　　者：阮永乐[1] 尹注增[1] 李俊华[1] 向莹[1] 郭晖[1] 钟山[1] 张炯[1] 郭晓伟[1] 陈实[1] 陈刚[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所卫生部/教育部器官移植重点实验室,武汉430030

出　　处：《中华器官移植杂志》2009年第12期740-744,共5页Chinese Journal of Organ Transplantation

基　　金：教育部新世纪优秀人才支持计划（NCET-06-0637）

摘　　要：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150（1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。Objective To investigate wh;thercotransplant 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 harvested for pathological examination and immunohistoehemical staining for CD3, Bcl-2 and HO-1. 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 control 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 associated with the inhibition of lymphocyte infiltration and the enhancement of the local expression of protective gene Bcl-2.

关 键 词：塞尔托利细胞 胰岛 移植 基因 bcl-2 血红素氧化酶 

分 类 号：R657.5[医药卫生—外科学]