Bile acid-induced expression of farnesoid X receptor as the basis for superiority of internal biliary drainage in experimental biliary obstruction

Abstract

Aims and objectives. The aim is to determine the efficacy of internal and external biliary drainage (ED) with special reference to the effect of bile acid on intestinal epithelium during experimental biliary obstruction. Methods. A total of 59 male Sprague Dawley rats were randomly assigned to four groups: (I) sham operation (SH); (II) obstructive jaundice (OJ); (III) OJ and ED; and (IV) OJ and internal biliary drainage (ID). The animals underwent surgical ligation of the bile duct on day 1. They were reoperated on day 8 for biliary drainage procedure. Blood cultures were obtained from portal vein and inferior vena cava on day 15. Samples were also drawn for serum total bile acid (TBA) and white blood cell (WBC) counts. The terminal ileum was harvested to study the tight junction-associated protein (“occludin”) and bile acid receptor (“farnesoid X receptor” [FXR]) using immunohistochemical method. Results. Serum TBA (118.9 ± 39.0 μmol/L) and WBC (11.4 ± 2.7 × 10⁹/L) were significantly increased (p = 0.001) after bile duct ligation as compared with SH rats (38.0 ± 15.0 μmol/L and 5.5 ± 1.0 × 10⁹/L, respectively; p = 0.001). The resulting mucosal lesion was high grade and the expressions of FXR and Occludin were decreased. After ED, there was slight decrease in total WBCs, whereas TBA levels declined significantly. The expression of FXR was minimal and Occludin showed no change (ED vs. OJ: p = 0.533). However, both WBC and TBA decreased after ID. The ileal structure, grade of mucosal lesion, and expression of FXR/Occludin were comparable with SH group (p > 0.05). The rate of bacterial translocation was: 57.1% (OJ); 62.5% (ID); and 80% (ED) with identical strains in cultures from the portal vein and inferior vena cava. Conclusion. Downregulation of TBA/FXR expression during biliary obstruction results in damage to intestinal epithelium. Unlike ED, ID restores FXR/Occludin expression in the terminal ileum through reappearance of intestinal bile acid, which thus appears to be a key factor in maintaining integrity of the epithelial barrier.

Key Words::

• bile acid
• farnesoid X receptor
• obstructive jaundice
• occludin

Acknowledgment

The authors thank Dr Aiqun Zhang and Huaiyin Shi for their technical assistance. They also extend their gratitude to members of the Hepatology Laboratory for critical review of the manuscript and their support during experimentation.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.