Fas/FasL表达和细胞凋亡在大鼠同种异体肝移植免疫中的作用  

Expression of Fas system and apoptosis in rat allografted liver

作　　者：刘玉兰[1] 刘峰[1] 孙君泓[2] 

机构地区：[1]北京大学人民医院消化内科北京大学肝移植中心,100044 [2]澳大利亚国家肝移植中心

出　　处：《中华普通外科杂志》2003年第2期99-101,共3页Chinese Journal of General Surgery

摘　　要：目的探讨Fas和Fas配体 (fasligand ,FasL)与细胞凋亡在大鼠肝移植免疫中的作用。方法分别用免疫组织化学法及原位杂交法 ,在移植后不同的时间点 (1、3、5、7d)检测Fas FasL、Bcl 2 Bax和细胞凋亡在不同的大鼠肝移植模型中的表达情况。结果肝急性排斥组与自发耐受组相比 ,肝细胞凋亡多 ,汇管区FasL表达高而肝细胞FasL表达低 [(2 1 5± 2 5 )个细胞vs.(39 5± 0 5 )个细胞 ,P <0 0 5 ],并且Fas[(47 0± 8 1)个细胞vs.(14 5± 0 8)个细胞 ,P <0 0 5 ]和Bax[(2 1 4± 1 1)个细胞vs.(9 4± 0 9)个细胞 ,P <0 0 5 ]表达高。子代组与肝急性排斥组各指标表达类似 ,半肝组与自发耐受组各指标表达类似。在移植后第 5天 ,汇管区凋亡指数与肝细胞FasL的表达呈正相关 (r =0 76 0 ,P <0 0 1) ,而与肝细胞Fas(r =- 0 75 9,P <0 0 1)、Bax的表达呈负相关 (r =- 0 840 ,P <0 0 1)。结论肝实质细胞的凋亡与肝急性排斥反应有关 ,而其Fas、Bax的高表达可能介导了肝实质细胞凋亡的发生 ;汇管区浸润细胞凋亡与肝自发耐受有关 ,肝细胞FasL的高表达可能介导了浸润细胞凋亡的发生。Objective To investigate the effects of apoptosis, Fas/FasL and Bax/Bcl-2 in rat liver allograft immune response. MethodsDifferent rat allograft models were established:(1)Acute liver allograft rejection group: PVG liver to Lewis rats; (2) Liver allograft tolerance group: PVG liver→DA rats; (3) F1(P/D)→D group: F1(PVG-DA) liver to DA rats; (4)HLTx(P/2→D)group: PVG/2 liver→DA rats. Liver samples were collected on days 1, 3, 5, 7 postoperatively (each n=3). Apoptosis was monitored by TUNEL(terminal deoxynucleotidyl transferase(TdT) mediated dUTP nick-end-labeling). The expressions of Fas/FasL and Bcl-2/Bax mRNA were examined by means of immunohistochemistry and in situ-hybridization respectively. Results Compared with liver allograft tolerance group, in acute liver allograft rejection group, the apoptosis cell numbers increased in hepatocytes, FasL expression was high in infiltrated cells in portal tract areas and low in hepatocytes, and the expression of Fas and Bax mRNA increased. The expression of molecules detected in F1(P/D)→D group was similar with those in acute liver allograft rejection. The expression of molecules detected in HLTx(P/2→D)group was similar with those in liver allograft tolerance group. On the fifth day postoperatively, the apoptosis index in portal tract areas had a positive correlation with the expression of FasL in hepatocyte and a negative correlation with the expression of Fas and Bax. Conclusions The high expression of FasL in infiltrated cells of portal tract areas, Fas and Bax in hepatocytes may be involved in rejection response. The high expression of apoptosis in infiltrated cells of portal areas, FasL in hepatocytes may relate with the establishment of tolerance.

关 键 词：肝移植 细胞死亡 CD95抗原 BCL-2基因 

分 类 号：R657.3[医药卫生—外科学]