关键词: PPARγ, 胆总管梗阻, 罗格列酮, 小肠屏障损伤

Abstract: Objective: To investigate the alteration of bile duct ligation (BDL) induced intestinal barrier dysfunction in mice and the protective effect of PPARγ pathway activation. Methods: The mice were divided into five groups randomly: Sham group, Sham+RGZ group, BDL group, BDL+RGZ group and BDL+RGZ+GW9662 group. All BDL group were established the model of bile duct ligation induced intestinal barrier dysfunction in mice. Mice were treated with RGZ, GW9662 or vehicle for 2 days before surgery and 5 days after. Blood and tissue samples were collected at the end of day 5. Intestinal morphological alteration were assessed, PPARγ associated oxidative stress and apoptosis and systematic inflammations of each group were determined by biochemical analysis; Protein expressions of PPARγ, Occludin, Bcl-2 and Bcl-xL in each group were evaluated by western blot. Results: BDL resulted in significant damage in intestinal barrier and severe systematic inflammation, accompanied by the protein expression of PPARγ, Occludin, Bcl-2 and Bcl-xL suppression (P<0.05); Pretreatment of RGZ significantly improved BDL induced intestinal injury and systematic inflammation, and up-regulated the protein expression of PPARγ, Occludin, Bcl-2 and Bcl-xL in the intestine(P<0.05). However, such protective effects were ameliorated in the BDL+RGZ+GW9662 group(P<0.05). Conclusion: PPARγ activation by rosiglitazone plays a protective role in intestinal barrier dysfunction induced by BDL in mice. This protective effect may be attributed to the anti-oxidant and anti-apoptosis properties of PPARγ.

Key words: PPARγ, common bile duct obstruction, rosiglitazone, intestinal barrier dysfunction