摘要目的 探讨法尼酯X受体(FXR)在肝硬化大鼠肝切除术后肝再生中的作用.方法 30只肝硬化大鼠肝切除术后按完全随机法分为对照组、胆酸组和消胆胺组饲养1周,每组10只.对照组给以标准饲料饲养,胆酸组给以含0.2%胆酸的饲料饲养,消胆胺组以含2%消胆胺的饲料饲养.1周后检测各组大鼠胆汁分泌速度及总胆汁酸(TBA)含量,检测肝功能、有丝分裂指数(MI)、增殖细胞核抗原(PCNA)标记指数和细胞核DNA含量,并应用RT-PCR和Western免疫印迹分别检测肝组织FXR、胆固醇7α羟化酶(CYP7A1)两者mRNA和蛋白的表达.结果 胆酸组胆汁分泌速度、TBA含量、血清白蛋白(ALB)含量、MI、PCNA标记指数、细胞核DNA含量均高于对照组(P<0.05),血清谷草转氨酶(AST)、谷丙转氨酶(ALT)均低于对照组(P<0.05).而消胆胺组胆汁分泌速度、胆汁TBA含量、血清ALB含量、MI、PCNA标记指数、细胞核DNA含量均低于对照组和胆酸组(P<0.05),血清谷草转氨酶(AST)、谷丙转氨酶(ALT)均高于对照组和胆酸组(P<0.05).胆酸组肝组织FXR mRNA和蛋白表达均高于对照组(mRNA:0.671±0.027比0.528±0.017,蛋白:0.702±0.039比0.566±0.020,P<0.05).肝组织CYP7A1mRNA和蛋白表达含量均低于对照组(mRNA:0.237±0.020比0.325±0.076,蛋白:0.264±0.015比0.325±0.084,P<0.05).而消胆胺组肝组织FXR mRNA(0.468±0.023)和蛋白表达(0.502±0.021)均低于对照组和胆酸组(P<0.05),肝组织CYP7A1 mRNA(0.411±0.021)和蛋白表达(0.476±0.018)则高于对照组和胆酸组(P<0.05).结论 胆汁酸与其受体FXR结合激活细胞内信号转导对肝硬化大鼠肝切除术后肝再生起重要作用,升高胆汁酸水平促进肝再生,降低胆汁酸水平则抑制肝再生.

abstractsObjective To evaluate the role of farnesoid X receptor(FXR) in liver regeneration after hepatectomy in cirrhotic rats. Methods Thirty cirrhotic rats with partial hepatectomy were randomly divided into control group (n=10),cholic acid group (n=10) and cholestyramine group (n=10) to be fed on a one-week diet. Control group was fed with normal diet,cholic acid group with 0.2% cholic acid,and cholestyramine group with 2% cholestyramine diet. One week after treatment,the rate of bile secretion,the total bile acids (TBA) content of bile,liver function,mitotic index (MI) of liver cell and proliferating cell nuclear antigen (PCNA) labeling index of hepatocyte and DNA contents in cell nuclear were determined. The mRNA and protein expressions of FXR and cholesterol 7α-hydroxylase (CYP7A1) in liver were determined by RT-PCR and Western blotting. Results Compared with the control group,the rate of bile secretion,the TBA content of bile,serum albumin (ALB),MI,PCNA labeling index and DNA contents in cell nuclear were significantly increased (P<0.05),serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly decreased (P<0.05) in the cholic acid group. While in the cholestyramine group,the rate of bile secretion,the TBA content of bile,serum ALB,MI,PCNA labeling index and contents of DNA in cell nuclear were significantly decreased (P<0.05),serum AST and ALT were significantly increased (P<0.05) as compared with the control group and cholic acid group. Compared with the control group,the mRNA and protein expressions of FXR were significantly increased (mRNA:0.671 ±0.027 vs 0.528±0.017,protein:0.702±0.039 vs 0.566±0.020,P<0.05),the mRNA and protein expressions of CYP7A1 were significantly decreased (mRNA:0.237±0.020 vs 0.325±0.076,protein:0.264±0.015 vs 0.325±0.084,P<0.05) in the cholic acid group. While in the cholestyramine group,the mRNA (0.468±0.023) and protein expressions (0.502±0.021) of FXR were significantly decreased (P<0.05),the mRNA (0.411 ±0.021 ) and protein expressions (0.476±0.018) of CYP7A1 were significantly increased ( P<0.05 ) as compared with the control group and cholic acid group. Conclusions Activation of intercellular signal transduction plays an important role in liver regeneration after hepatectomy in cirrhotic rats by binding of bile acid to its receptor FXR. Elevated or reduced bile acid levels may be associated with accelerated or inhibited liver regeneration.