基于Bak/Bax/Caspase-9通路探讨小檗碱对溃疡性结肠炎小鼠疗效的机制研究

Mechanistic study of the therapeutic effect of berberine on ulcerative colitis in mice based on the Bak/Bax/Caspase-9 pathway

目的探讨小檗碱通过Bak/Bax/Caspase-9通路对溃疡性结肠炎(ulcerative colitis,UC)小鼠保护作用的机制。方法将32只C57BL/6小鼠随机分为正常组、模型组、美沙拉嗪组、小檗碱组,每组8只。除正常组外,其余组予以3%葡聚糖硫酸钠盐(dextran sulfate sodium salt,DSS)构建UC小鼠模型。记录各组小鼠的疾病活动指数(disease activity index,DAI)评分及体重;测量结肠长度、脾脏指数;通过苏木精-伊红染色观察结肠、脾脏组织病理变化;利用qRT-PCR和Western blot法分别检测结肠组织中Bak、Bax、Caspase-9的mRNA和蛋白表达。结果与模型组比较,小檗碱组小鼠的DAI评分与脾脏指数显著降低(P<0.05),结肠及脾脏病理损伤显著缓解,体重变化率和结肠长度显著升高(P<0.01),结肠组织中Bak、Bax、Caspase-9的mRNA和蛋白表达显著降低(P<0.05)。结论小檗碱能够降低UC小鼠的炎症反应,改善结肠和脾脏病理损伤,其作用可能与调控Bak/Bax/Caspase-9通路相关。

Objective This study aimed to investigate the protective effect of berberine on mice with ulcerative colitis(UC)and the involvement of the Bak/Bax/Caspase-9 pathway.Methods A total of thirty-two C57BL/6 mice were divided into four groups:normal group,model group,mesalazine group,and berberine group.The mice were randomly assigned to these groups for the study.The UC mouse model was induced in all groups using 3%dextran sulfate sodium salt(DSS).Disease activity index(DAI)score and body weight were recorded daily.Colon length and spleen index were measured.HE staining examined colon and spleen tissue changes.Bak,Bax,and Caspase-9 mRNA/protein expression in colon was measured via qRT-PCR/Western blot.Results Compared to the model group,the berberine group exhibited a significant reduction in the DAI score and spleen index(P<0.05),along with improved colon and spleen pathological damage,there were significant increases in percentage of body weight change and colon length(P<0.01),mRNA and protein expression of Bak,Bax,and Caspase-9 in colon tissues were significantly decreased in the berberine group(P<0.05).Conclusion Berberine reduced inflammation and improved colon and spleen pathological damage in UC mice,potentially through modulation of the Bak/Bax/Caspase-9 pathway.