原儿茶酸调控PPARγ通路对小鼠胆总管梗阻肠屏障损伤的保护作用

Protective effects and mechanisms of protocatechuic acid on common bile duct obstruction induced intestinal barrier dysfunction in mice

目的:研究原儿茶酸对小鼠胆总管梗阻肠屏障损伤的保护作用及作用机制。方法:构建小鼠胆总管结扎(BDL)术继发小肠屏障损伤模型。将小鼠随机分为假手术组、模型组、模型+原儿茶酸低、中、高剂量(20 mg/kg、40 mg/kg、80 mg/kg)组,各给药组于术前2天给至术后5天腹腔注射相应剂量原儿茶酸。第5天末处死小鼠,检测小肠形态学、小肠PPARγ通路相关氧化应激和细胞凋亡指标及全身炎症指标;利用Western blot检测小肠PPARγ、Occludin和Bcl-2蛋白表达。结果:模型组小鼠较对照组病理损伤评分显著升高,血清TNF-α、IL-6和TB显著升高,小肠组织SOD、GSH、GSH-Px降低,MDA升高;小肠细胞凋亡显著。原儿茶酸腹腔注射原儿茶酸20 mg/kg、40 mg/kg、80 mg/kg组可不同程度改善上述指标变化,并呈剂量依赖趋势。模型组较对照组小肠PPARγ、Occludin、Bcl-2表达降低;原儿茶酸处理组较模型组可显著提升上述蛋白在小肠组织中的表达。结论:原儿茶酸能在小鼠胆总管梗阻肠屏障损伤中发挥保护作用,其机制可能与提高小肠PPARγ表达,减轻小肠组织的氧化应激和细胞凋亡相关。

Objective： To investigate the protective effect of protocatechuic acid（PCA） on common bile duct obstruction induced intestinal barrier dysfunction in mice and its mechanism.Methods： Establish the model of bile duct ligation（BDL） induced intestinal barrier dysfunction in mice.The mice were divided into five groups randomly： sham group,model group,model ＋ PCA（20 mg / kg,40 mg / kg,80 mg / kg） group.Mice were treated with PCA for 2 days before surgery and 5 days after.Blood and tissue samples were collected at the end of day 5.Intestinal morphological alteration,PPARγ associated oxidative stress and apoptosis in each group were determined;Systematic inflammation of each mice were assessed;Protein expression of PPARγ,Occludin and Bcl-2 in each group were evaluated.Results： BDL resulted in significant damage in intestinal barrier and severe systematic inflammation,accompanied by the protein expression of PPARγ,Occludin and Bcl-2 suppression;Pretreatment of PCA significantly improved BDL induced intestinal injury and systematic inflammation,and up-regulated the protein expression of PPARγ,Occludin and Bcl-2 in the intestine.Conclusion： PCA has significant protective effects on bile duct ligation induced intestinal barrier dysfunction in mice.This protective effect may be attributed to the PCA induced PPARγ pathway activation and the anti-oxidant and anti-apoptosis properties of PPARγ.