基因转移CTLA4-Ig对异种胰岛移植排斥反应的影响.pdfVIP

2008；28(2) 南方医科大学学报 South Med Univ) ·159· 基因转移CTLA4一Ig对异种胰岛移植排斥反应的影响 张 剑 ，陈规划 ，陆敏强 ，翁建平 ，杨 扬 ，蔡常洁 ，许 赤 ，李 华 ( 中山大学附属第三医院肝脏移植中心， 广东 广州 510630； 中山大学附属第一医院．广东 广州 510080) 摘要：目的探讨基因转移细胞毒性T淋巴细胞相关抗原4免疫球蛋白(CTLA4．Ig)对异种胰岛移植排斥反应的影响。 方法用携带基因CTLA4．Ig的重组腺病毒转染人胰岛细胞，植入糖尿病大鼠肾胞膜下，建立人一大鼠异种胰岛移植模 型，观察糖尿病大鼠移植后血糖变化、生存情况及移植物病理形态学改变。检测移植物CTLA4．Ig、胰岛素的表达和移植 大鼠IL-2、TNF．ot的水平变化。结果 (1)糖尿病大鼠胰岛移植后2 d血糖降至正常，对照组和转染组血糖平均分别在 移植后 8 d和25 d升高。(2)转染组移植物存活时间(28±6)d，较对照组(10~2)d显著延长(t=10．52，P0．01)。(3)移植 大鼠生存时间：转染组(48±8)d显著长于对照组(21±6)d(t=12．23，P0．01)。(4)对照组在移植后 l周内，Ⅱ，2、TNF—ot 水平均急尉上升，较移植前显著升高(PO．01)；转染组则较移植前下降。(5)转染组移植物可见CTLA4． 和胰岛素的表 达。结论基因转移CTLA4．Ig可抑制异种胰岛移植排斥反应，延长移植大鼠和移植物的存活时间。 关键词：胰岛移植；糖尿病；免疫耐受；CTLA4．Ig 中图分类号：R392．4；R587 文献标识码：A 文章编号：l673-4254(2008)02．0159-03 Effect of CTLA4-Ig gene transfer on rejection of rat islet xenografts ZHANG Jian’，CHEN Gui-hua’，LU Min-qiang‘，WENG Jian-ping2,YANG Yang’，CAI Chang-jie‘，XU Chi‘，LI Hua‘ 。Organ Transplantation Center，111矾 Affiliated Hospital of Sun Yat-sen University，Guangzhou 5 10630，China；ZFirst Affiliated Hospital ofSunYat-senUniversity,Guangzhou 510080，China Abstract：Objective To investigate the effect ofcytotoxic T lymphocyte-associated antigen 4 immunoglobulin (CTLA4-Ig) gene transfer on rejection of rat islet xenografls．Methods Human islets wore infected with the recombinant adenoviruses containing CTLA4-Ig gene， and the transduced islets were transplanted under the left kidney capsule of diabetic rats to establish rat models bearing human-rat islet xenografls．The blood sugar ofthe rats receiving the transplantation was measured and the xenografls and host survival were observed after transplantation．The morphological changes ofgrafts were examined， in which the expression of CTLA4-Ig and insulin wore also detected by immunohistochemical staining and the cytokines were