【摘要】 目的探讨细胞毒性T淋巴细胞相关抗原4(CTLA4-Ig)融合蛋白对同种异体肝脏移植免疫耐受的诱导作用及机理。方法利用大型哺乳动物猕猴作为研究对象,建立同种异体原位肝脏移植模型。同种异体原位肝脏移植对照组及CTLA4-Ig组各5只。观察术后生存时间,检测肝功能、IL-2、IL-10、排斥反应的病理学分级和术后肝脏细胞凋亡指数。结果对照组平均存活时间为6.57 d,CTLA4-Ig组平均存活时间为14.92 d(P<0.05)。肝功能变化:对照组术后ALT明显升高,Alb则明显降低;CTLA4-Ig组ALT及Alb均维持于正常稳定水平。细胞因子变化:术后3 d起,对照组循环血中IL-2表达水平相对较高,而CTLA4-Ig组IL-10的表达水平较对照组高。移植物病理排斥反应分级:在移植术后CTLA4-Ig组排斥反应程度明显比对照组轻。对照组术后3 d起肝脏细胞凋亡指数较CTLA4-Ig组明显升高。结论CTLA4-Ig融合蛋白可诱导移植后免疫耐受,延长受体生存时间。细胞因子IL-2或者IL-10可作为监测移植排斥反应或者免疫耐受的实验室指标之一。更多还原

【Abstract】 Objective To explore the effect of cytotoxic T lymphocyte-associated antigen 4(CTLA4-Ig) fusion protein on the function of orthotopic liver allograft.Methods Orthotopic liver allograft models of rhesus monkeys were established in this study.The survival time,liver function and morphologic changes of graft were observed,respectively.The levels of IL-2 and IL-10 were detected by ELISA.Apoptosis was monitored by TUNEL.Results The average survival of control group was 6.57 d,while the average survival of CTLA4-Ig group was 14.92 d,which was statistically prolonged(P<0.05).Serum ALT level was highly increased,and Alb level decreased obviously in control group.While the levels of ALT and Alb kept in normal in CTLA4-Ig group.After day 3-7,the expressions of IL-2 were highly expressed in control group,while the expressions of IL-10 in CTLA4-Ig group were higher than those of control group.The severity of rejection reaction after day 3 was weaker in CTLA4-Ig group than that of control group by histological assessment.The apoptosis index after day 3 in the liver cells was highly increased in control group as compared with the CTLA4-Ig group.Conclusions CTLA4-Ig fusion protein therapy can induce immunotolerance and prolong the survival of recipients.The increasing of cytokines IL-2 or the decreasing of cytokines IL-10 may be one of the laboratory indexes in monitoring immunotolerance of transplantation.更多还原