The role of farnesoid X receptor in liver regeneration after hepatectomy in cirrhotic rats

Objective 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. Key words: Liver cirrhosis; Hepatectomy; Liver regeneration; Farnesoid X receptor; Cholesterol 7α-hydroxylase