小檗碱对2型糖尿病大鼠肠壁通透性和肠道菌群的影响  

The effect of berberine on intestinal permeability and gut microbiota in rats with type 2 diabetes

作　　者：赵洋[1,2] 栾海艳 李晶[1] 王肖烨[1,2] 高璐 张昆 ZHAO Yang;LUAN Haiyan;LI Jing;WANG Xiaoye;GAO Lu;ZHANG Kun(Basic Medicine College,Jiamusi University,Jiamusi,Heilongjiang 154007,China;Key Laboratory of Microbial-Immune Mediation Network and Related Diseases of Heilongjiang Province,Jiamusi,Heilongjiang 154007,China;不详)

机构地区：[1]佳木斯大学基础医学院,黑龙江佳木斯154007 [2]黑龙江省微生物−免疫调解网络与相关疾病重点实验室

出　　处：《中国微生态学杂志》2025年第2期139-146,154,共9页Chinese Journal of Microecology

基　　金：黑龙江省教育厅基本科研业务费基础研究团队项目(2022-KYYWF-0656)。

摘　　要：目的探究小檗碱(BBR)是否能改善糖尿病诱发的肠壁损伤和菌群紊乱,为BBR在2型糖尿病(T2DM)治疗方面的应用提供实验基础。方法将6~7周龄40只健康清洁级雄性SD大鼠称重后随机分为空白对照组(NC组)、高脂高糖组(HFG组)、糖尿病组(DM组)及黄连素组(BBR组),每组10只。造模成功后取各组大鼠结肠、回肠进行肠壁通透性观察,取各组大鼠粪便样本进行16S rRNA基因测序。结果HFG组、DM组大鼠结肠组织黏膜出现不同程度病理变化,BBR组大鼠结肠组织黏膜有改善;DM组大鼠肠脂肪酸结合蛋白(I-FABP)、法尼醇X受体(FXR)mRNA的表达水平降低(F=6.698,P<0.010;F=2.265,P<0.001),而BBR组的表达水平增强(F=3.449,P<0.050;F=6.728,P<0.010);Alpha和beta多样性分析显示,组间存在显著性肠道微生物群落差异,DM组大鼠肠道菌群系统进化多样性(Faith's)指数低于NC组(t=33.000,P=0.015),BBR组大鼠肠道菌群丰富度低于DM组(t=34.000,P=0.009)。与NC组相比,DM组大鼠肠道菌群物种总数和丰度降低,厚壁菌门_C(t=−3.502,P=0.004)、脱硫杆菌门(t=2.537,P=0.012)相对丰度升高,Muribaculaceae菌科(t=−2.442,P=0.015)、瘤胃球菌属_B(t=2.739,P=0.006)相对丰度降低;与DM组相比,BBR能降低T2DM大鼠厚壁菌门_C(t=−2.394,P=0.018)、脱硫杆菌门(t=2.854,P=0.005)相对丰度,升高Muribaculaceae菌科(t=2.739,P=0.006)、瘤胃球菌属_B(t=2.968,P=0.005)相对丰度。结论BBR可以改善DM组大鼠肠道菌群结构。Objective To observe whether berberine(BBR)could improve diabetes-induced intestinal wall disruption and flora disorders,and provide an experimental basis for the application of BBR in the treatment of T2DM.Methods Forty healthy clean-grade male SD rats at 6-7 weeks of age were weighed and randomly divided into blank control(NC)group,high-fat-high-glucose(HFG)group,diabetes(DM)group,and BBR group,with 10 rats in each group.After successful modelling,the colon and ileum samples of rats in each group were taken for observation of intestinal wall permeability,and fecal samples in each group were taken for 16S rRNA gene sequencing.Results The mucosa of colonic tissues of rats in HFG and DM groups showed different degrees of pathological changes,and there was improvement in the mucosa of colonic tissues of rats in BBR group;the expression levels of intestinal fatty acid binding protein(I-FABP)and farnesol X receptor(FXR)mRNA were reduced in rats in DM group(F=6.698,P<0.010;F=2.265,P<0.001),and the expression in BBR group was enhanced(F=3.449,P<0.050;F=6.728,P<0.010);Alpha and beta diversity analyses showed that there were significant intestinal microbial community differences between the groups,and the phylogenetic diversity(Faith's)index of the intestinal flora of the rats in the DM group was lower than that of the NC group(t=33.000,P=0.015),and the rat intestinal flora richness was lower than that of DM group(t=34.000,P=0.009).Compared with the NC group,the total number of species and abundance of rat intestinal flora were lower in the DM group,with elevated relative abundance of Firmicutes_C(t=−3.502,P=0.004),Desulfovibrio(t=2.537,P=0.012),and increased relative abundance of Muribaculaceae family(t=−2.442 P=0.015),and Rumenococcus spp._B(t=2.739,P=0.006)decreased in relative abundance;BBR decreased the relative abundance of Firmicutes_C(t=−2.394,P=0.018),Desulfovibrio(t=2.854,P=0.005),and elevated the relative abundance of relative abundance of Muribaculaceae(t=2.739,P=0.006),Ruminalococcus spp._B(t=2.968,P=0

关 键 词：小檗碱 2型糖尿病 肠道菌群 肠壁屏障 16S rRNA 

分 类 号：R587.1[医药卫生—内分泌]