title: Bile acid-induced expression of farnesoid X receptor as the basis for superiority of internal biliary drainage in experimental biliary obstruction.
abstract: OBJECTIVE
  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 × 10(9)/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 × 10(9)/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.
  
  
  CONCLUSIONS
  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.
authors: Department of Gastroenterology-Hepatology, People's Liberation Army General Hospital (PLAGH), Beijing, Peoples' Republic of China.
authors: Lili
authors: L
authors: Wu
authors: Wen
authors: W
authors: Li
authors: Zikai
authors: Z
authors: Wang
authors: Zuohui
authors: Z
authors: Yuan
authors: Qurratulain
authors: Q
authors: Hyder
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D004322:Drainage / Q000379:methods; D007082:Ileum / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D041781:Jaundice, Obstructive / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D007958:Leukocyte Count; D008026:Ligation; D008297:Male; D062793:Occludin / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers; D062793:Occludin; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated