Expression of farnesoid X receptor in the liver of rats with obstructive jaundice and the effect of CDCA

Objective To evaluate the effect of chenodeoxycholic acid (CDCA) in the treatment of hepatobiliary disease, and to prove a new targets of FXR as treatment drug for obstructive jaundice. Methods Seventy-two 4-weeks-old male Sprague-Dawley (SD) rats were enrolled in this study. Forty-eight of the rats had the common bile duct ligated above the duodenum, and then cut and sutured to establish the rat model of bile duct obstruction (the study group). The other 24 rats had the common bile duct separated and then sutured (the control group). The morphological changes of liver tissue 1 d, 3 d, 7 d, and 14 d after bile duct obstruction were observed. The alanine aminotransferase (ALT), total bilirubin (TB) and total bile acid (TBA) in serum were detected. The expression of FXR in different stage of bile duct obstruction was observed by immunohistochemistry. At the same time, the role of CDCA played in the process of rat bile duct obstruction was investigated. Results After bile duct obstruction, the rats suffered intrahepatic cholangiectasis, fibroustissue hyperplasia, which relieved 14 d later. The levels of ALT, TB and TBA in serum were significantly increased as the increase of time after obstruction, reaching the peak on the 7th day after obstruction (P0.05). The levels were decreased significantly on the 14th day after obstruction. CDCA could reduce the level of ALT, TB and TBA in serum to varying degrees. In addition, with the extension of time after obstruction, the expression of FXR was up-regulated reached the peak on the 7th day, which indicates that CDCA could inhibit the expression of FXR obviously. Conclusion Bile duct obstruction can lead to liver injury and fibroustissue hyperplasia, the degree of which is positively correlated between the level of ALT in serum. Bile duct obstruction leads to the increase of bile acid concentration, which stimulates the expression of FXR. FXR agonist (CDCA) can relieve the liver damage after biliary obstruction.