CTLA4-Ig基因对大鼠肝移植后免疫细胞浸润及细胞凋亡的影响  

Role of adenovirus mediated CTLA4-Ig gene in the immune cells infiltration and cell apoptosis in murine liver transplantation

作　　者：蒋国平[1] 沈克震[1] 郑树森[1] 贾长库[1] 章爱斌[1] 冯晓文[1] 王伟林[1] 

机构地区：[1]浙江大学医学院附属第一医院肝胆外科卫生部多器官联合移植研究重点实验室,杭州310003

出　　处：《中华普通外科杂志》2005年第8期483-485,共3页Chinese Journal of General Surgery

基　　金：浙江省自然科学基金资助项目(编号300503);浙江省教育厅资助项目(20020792)

摘　　要：目的研究腺病毒介导的细胞毒性T淋巴细胞相关抗原4-Ig(cytolyticT-lymphocyteassociatedantigen4-Ig,CTLA4-Ig)基因对大鼠肝移植后移植物中免疫细胞浸润和细胞凋亡的影响。方法将大鼠原位肝移植模型分为排斥对照组、环孢素A(CsA)组和CTLA4-Ig组。分别于术后1,3,5,7,12d,用免疫组织化学法和缺口末端标记技术(TUNEL法)分别测定移植物中CTLA4-Ig基因的表达和巨噬细胞、CD8+T细胞浸润及细胞凋亡,并以病理形态学变化作参照。结果静脉注射重组CTLA4-Ig基因腺病毒7d后,大鼠肝脏CTLA4-Ig稳定表达,在肝移植60d后仍呈阳性;CTLA4-Ig组汇管区巨噬细胞、CD8+T细胞浸润明显较排斥对照组少;细胞凋亡指数在术后3、5和7d明显低于排斥对照组(P<0·01),汇管区巨噬细胞、CD8+T细胞浸润数和凋亡指数与排斥反应分级均显著相关。结论重组CTLA4-Ig基因腺病毒经静脉一次给药后能在大鼠肝脏稳定表达,并通过抑制移植物中免疫细胞浸润及移植物细胞凋亡,抑制移植后急性排斥反应。Objective To investigate the role of B7/CD28 eostimulation pathway blockade with adenovirus-mediated CTLA4-Ig gene in macrophage and CD8^＋ T cell infiltration and cell apoptosis in murine liver transplantation. Methods Rat pairs were divided into three groups： SD-to-Wistar transplantation control group, CsA-treated group and CTLA4-Ig-treated group. IHC and TUNEL were used to analyze the expression of CTLA4-Ig gene in liver and immune cells infiltrate and cell apoptosis in liver grafts. Pathology was done on all harvested grafts. Results CTLA4-Ig gene expression was positive in the donor liver on day 7 after administering adenovirus-mediated CTLA4-Ig gene via vein, and remained positive until day 60 after liver transplantation. Infiltration of immune cells in CTLA4-Ig-treated group was less than that in rejection control group, the apoptotic index of rejection group on day 3,5,7 was significantly higher than those of CTLA4-Ig-treated. Conclusions CTLA4-Ig gene was constantly expressed in the donor liver after single intravenousely injection into rats using adenovirus as vector. Adenovirus-mediated CTLA4-Ig gene therapy can inhibit infiltration of immune cells and apoptosis in grafts, thus prolonging the survival of recipients.

关 键 词：CTLA4-Ig基因 大鼠 肝移植 免疫细胞 细胞浸润 细胞凋亡 

分 类 号：R657.3[医药卫生—外科学]