Moleculer mechanisms of cholestyramine in promoting bile acid synthesis

Objective To study the possible mechanisms of cholestyramine promoting bile acid synthesis in vitro.Methods Twenty New Zealand white rabbits were divided into cholestyramine group (n=10) and control group (n=10). Each rabbit in treatment group was administered with cholestyramine 1 g/kg per day for 2 weeks by gavage. The serum bile acids level, serum cholesterol level and activity and mRNA expression of cholesterol 7-alpha-dydroxylase (CYP7A1) in liver tissues after treatment were assessed. The mRNA expression of farnesoid X receptor (FXR) target genes, short heterodimer partner (SHP) and bile salt export pump (BSEP) in liver tissues, and the mRNA expression of LDL-R in liver tissues were also detected. Results The serum cholesterol level decreased 10.25% in cholestyramine group, while the serum bile acids level had no changes. In the liver tissues, the activity and mRNA expression of CYP7A1 significantly increased (P0.05), the mRNA expression of FXR target gene SHP and BESP significantly decreased (P0.01),and the mRNA expression of LDL-R significantly increased (P0.05)as compared with those in the controls.Conclusion Cholestyramine can decrease the reAbsorption of bile acid (the ligand of FXR) to the liver where inactivates FXR, and activates CYP7A1 and promotes the synthesis of bile acid, then maintains the bile acid level and lowers serum cholesterol.