阻断ICOS对小鼠移植胰岛功能影响的实验研究  

Effect of blockade of inducible costimulator on pancreatic islet allograft function in mice

作　　者：赵国华[1] 张佳林[1] 许国岩 钟鑫平[1] 杨蕾[1] 李铁民[1] 程颖[1] 刘永锋[1] 

机构地区：[1]中国医科大学附属第一医院器官移植研究所 [2]解放军65735医院内科

出　　处：《中国医科大学学报》2006年第6期591-593,共3页Journal of China Medical University

基　　金：辽宁省自然科学基金资助项目(20042096)

摘　　要：目的:在小鼠胰岛移植模型基础上,通过阻断可诱导共刺激分子(ICOS),探讨ICOS单克隆抗体(ICOS mAb)对移植胰岛功能的影响。方法:供体为近交系昆明小鼠,受体为C57小鼠。受体小鼠随机分成5组,每组10只。假手术组:受体小鼠仅行开腹手术,不行胰岛移植;对照组:单纯胰岛移植,不给ICOS mAb;实验1、2、3组:分别于胰岛移植后1、3、5 d腹腔内注射ICOSmAb 50、100、200μg/kg。观察小鼠胰岛移植后移植物存活时间和移植胰岛病理改变,流式细胞仪检测ICOS在T淋巴细胞上的表达。结果:实验2组小鼠移植胰岛存活时间和实验3组相同,统计学分析无显著性差异,而较对照组及实验1组明显延长(P<0.05)I,COS在移植术后7 d受体小鼠T淋巴细胞上表达明显上调。结论I:COS分子在小鼠同种异体胰岛移植排斥反应中表达上调,参与了排斥反应的发生。ICOS mAb通过阻断ICOS共刺激信号途径,诱导小鼠同种异体胰岛移植免疫耐受,减轻排斥反应,延长移植胰岛有功能存活时间。ICOS mAb的最佳给药剂量为100μg/kg。Objective： To study the effect of inducible costimuhtor monoclonal antibody（ICOS mAb）on the function of pancreatic islet allograft in mice by blocking ICOS. Methods： Isolated islets of Kunming species mice were transplanted into streptozotocin-induced diabetic C57 mice. The C57 mice were randomly divided into 5 groups （n=10）： sham operation group, control group, and experimental groups 1,2,and 3. The mice in experimental groups 1,2,and 3 were intraperitoneally injected with 50, 100, and 200 μg/kg of ICOS mAb 1,3,and 5 days after pancreatic islet transplantation. The survival time and pathological changes of pancreatic islet were observed, and the expression of ICOS on T lymphocytes was detected by flow cytometry. Results： No significant difference in the survival time of pancreatic islet allograft was found between experimental groups 2 and 3. Compared with experimental group 1 and control group, the survival time of pancreatic islet allograft in experimental groups 2 and 3 were significantly longer （P 〈 0.05 ）, and the expression of ICOS on T lymphocytes was significantly higher 7 days after the pancreatic islet transplantation. Conclusion： ICOS mAb may induce the immunologic tolerance, alleviate the rejection, and prolong the survival time of pancreatic islet allograft by blocking ICOS pathway. The best dose of ICOS mAb is 100 μg/kg.

关 键 词：胰岛移植 排斥反应 共刺激信号 可诱导共刺激分子单克隆抗体 

分 类 号：R617.5[医药卫生—外科学]