罗格列酮减轻小鼠胆总管梗阻致小肠屏障损伤

Rosiglitazone ameliorates intestinal barrier dysfunction induced by bile duct obstruction in mice

目的研究胆总管梗阻对小鼠小肠屏障的损伤作用及罗格列酮激活PPARγ对胆总管梗阻小鼠小肠屏障功能的保护作用。方法将小鼠随机分为假手术组、假手术+罗格列酮(PPARγ激动剂)组、模型组、模型+罗格列酮组及模型+罗格列酮+GW9662(PPARγ抑制剂)组。各模型组构建小鼠胆总管结扎(BDL)术致继发性小肠屏障损伤模型。于术前2 d至术后5 d给相应药物。第5天末处死小鼠,检测小肠形态学、生化分析法检测小肠PPARγ通路相关氧化应激和凋亡指标及全身炎症指标;Western blot法检测小肠PPARγ、Occludin、Bcl-2和Bcl-x L蛋白表达。结果模型组小鼠较对照组发生显著肠道屏障损伤和全身炎症损伤,同时肠道PPARγ、Occludin、Bcl-2和Bclx L蛋白表达降低(P<0.05);模型+罗格列酮组较模型组损伤程度较低,同时上述蛋白表达升高(P<0.05);模型+罗格列酮+GW9662组较模型+罗格列酮组损伤程度加重,上述蛋白表达降低(P<0.05)。结论罗格列酮激活PPARγ可减轻胆总管梗阻小鼠小肠屏障损伤,表现为减轻形态学损伤、PPARγ通路相关氧化应激及细胞凋亡。

Objective To investigate the alteration of bile duct ligation （BDL） induced intestinal barrier dysfunction in mice and the potential 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.The model was developed into intestinal barrier dysfunction by bile duct ligation 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）.Conclusions 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.