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目的 观察转FasL基因的树突状细胞 (DC)体内注射诱导大鼠肝移植免疫耐受作用 ,并研究其机制。方法 用“二袖套法”行受体为Wistar大鼠肝移植 36例 ,并随机分为 3组 :①对照组(n =12 ) ;②环孢霉素治疗组 (n =12 ) ;③转FasL基因治疗组 (n =12 ) ,腹腔注射转FasL基因的树突状细胞。手术后 7d分别杀死各组 4只大鼠 ,用原位末端标记法及透射电镜观察移植肝细胞及肝脏内淋巴细胞凋亡 ,其余大鼠用于观察生存期。结果 对照组大鼠在 9～ 15d迅速死亡 ,TUNEL及电镜观察发现肝细胞变性坏死明显 ;而环孢霉素治疗组及转FasL基因治疗组免疫排斥反应轻微 ,移植后大鼠已存活超过 6个月 ,原位末端标记法及透射电镜均发现FasL基因治疗组肝脏内浸润淋巴细胞凋亡明显。结论 转FasL基因DC细胞治疗能有效地诱导肝移植免疫耐受 ,其机制是诱导了肝脏内浸润淋巴细胞凋亡
Objective To observe the immunological tolerance induced by dendritic cells (DCs) transfected with FasL gene in rats and to investigate its mechanism. Methods Twenty-six Wistar rats were randomly divided into three groups: ① control group (n = 12); ② cyclosporin-treated group (n = 12); ③ The FasL gene therapy group (n = 12) was injected intraperitoneally with dendritic cells transfected with FasL gene. At 7 days after operation, 4 rats in each group were killed. Apoptosis in transplanted hepatocytes and liver lymphocytes was observed by in situ terminal labeling and transmission electron microscopy. The remaining rats were used to observe the survival. Results The rats in the control group died rapidly from 9 to 15 days. The degeneration and necrosis of hepatocytes were found by TUNEL and electron microscopy. The immunosuppression in the cyclosporin-treated group and the trans-FasL gene-treated group was slight. After the transplantation, the rats survived more than 6 Month, in situ terminal labeling and transmission electron microscopy were found FasL gene therapy group of liver infiltration of lymphocytes apoptosis significantly. Conclusion The treatment of FasL transgenic DC cells can effectively induce the immune tolerance of liver allografts. The mechanism is that apoptosis of infiltrating lymphocytes in the liver is induced