基于肠道菌群和代谢组学探讨抵当芪桂汤改善大鼠2型糖尿病作用机制  

Exploration on the Mechanism of Didang Qigui Decoction in Improving Type 2 Diabetes Mellitus in Rats Based on Intestinal Flora and Metabolomics

作　　者：程都 郭怡佳 张潇 雷莉妍 梁艳妮 王征 杨景锋[1] CHENG Du;GUO Yijia;ZHANG Xiao;LEI Liyan;LIANG Yanni;WANG Zheng;YANG Jingfeng(College of Basic Medical Science,Shaanxi University of Chinese Medicine,Xianyang 712046,China;Collaborative Innovation Center for Chinese Medicinal Resources Industrialization by Shaanxi Province,Xianyang 712083,China)

机构地区：[1]陕西中医药大学基础医学院,陕西咸阳712046 [2]陕西省中药资源产业化协同创新中心,陕西咸阳712083

出　　处：《中国中医药信息杂志》2024年第5期76-84,共9页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：陕西省重点产业创新链项目(2018ZDCXL-SF-01-02-02);陕西高校青年科技创新团队(2019年);陕西省教育厅重点科学研究计划(20JY011、20JY012)。

摘　　要：目的基于肠道菌群和代谢组学探讨抵当芪桂汤治疗2型糖尿病(T2DM)的可能作用机制。方法采用高糖高脂饮食联合腹腔注射链脲佐菌素诱导T2DM大鼠模型,将大鼠分为空白对照组、模型组、二甲双胍组和中药低、中、高剂量组,每组10只,给药组分别予相应药液灌胃6周。测定大鼠空腹血糖(FBG)及血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶酶(ALT)含量,HE染色观察大鼠胰腺组织、结肠组织形态,16SrRNA测定肠道微生物群落组成及相对丰度,非靶向代谢组学对血清代谢物进行分析,采用正交偏最小二乘-判别分析(OPLS-DA)筛选潜在差异代谢物,MetaboAnalyst5.0平台分析代谢物的代谢通路,对肠道菌群及血清代谢结果进行联合分析。结果与空白对照组比较,模型组大鼠体质量显著降低,FBG显著升高,血清TG、TC、LDL-C、ALT、AST含量显著升高(P<0.01);胰岛结构严重萎缩变形、边界模糊不清,胰岛细胞排列紊乱,部分出现空泡变性,核碎裂或溶解消失;结肠结构破坏明显,上皮细胞脱落,炎性细胞浸润。与模型组比较,中药低、中、高剂量组大鼠FBG显著降低,血清TG、TC、LDL-C、AST、ALT含量显著降低(P<0.01),胰岛形态不同程度改善,结肠组织炎性细胞浸润减轻。16SrRNA测序结果显示,抵当芪桂汤可调节T2DM大鼠肠道菌群结构,提高Chao1、observed_species、PD-whole-tree、Simpson谱系多样性指数,上调厚壁菌门、放线菌门等相对丰度,下调拟杆菌门相对丰度,增加乳杆菌属、双歧杆菌属、Lachnoclostridium属等益生菌相对丰度。血清代谢组学分析共筛选出1-十四酰-2-羟基卵磷脂、N-甲基烟酰胺、乳清酸、丙氨酸、D-甘露糖等12个潜在差异代谢物,涉及D-精氨酸和D-鸟氨酸代谢、苯丙氨酸代谢、甘油磷脂代谢、嘧啶代谢4条代谢通路。相�Objective To investigate the possible mechanism of Didang Qigui Decoction in the treatment of type 2 diabetes mellitus(T2DM)based on intestinal flora and metabolomics.Methods T2DM rat model was induced by high sugar and high fat diet combined with STZ intraperitoneal injection.The rats were divided into blank control group,model group,Metformin group,Didang Qigui Decoction low-,medium-and high-dosage groups,with 10 rats in each group.The medication groups was given corresponding medicine for gavage for 6 weeks.The fasting blood glucose(FBG)and total cholesterol(TC),total triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT)in serum were determined.HE staining was used to observe pancreatic and colon tissue morphology in rats.16S rRNA was used to determine the composition and relative abundance of gut microbiota,and non-targeted metabolomics was used to analyze serum metabolites.Orthogonal partial least squares-discriminant analysis(OPLS-DA)was used to screen for potential differential metabolites,MetaboAnalyst 5.0 platform was used to analyze metabolic pathways of metabolites,and perform joint analysis on gut microbiota and serum metabolism results.Results Compared with the blank control group,the model group showed a significant decrease in body mass,a significant increase in FBG,and a significant increase in serum TG,TC,LDL-C,ALT and AST contents(P<0.01);the structure of pancreatic islets was severely atrophied and deformed,with unclear boundaries,disordered arrangement of pancreatic islet cells,partial vacuolar degeneration,nuclear fragmentation or dissolution disappearance;the colon structure was significantly damaged,with epithelial cells shedding and inflammatory cells infiltrating.Compared with the model group,the FBG of rats in the Didang Qigui Decoction low-,medium-and high-dosage groups were significantly decreased,and the contents of serum TG,TC,LDL-C,AST and ALT were significantly decreased

关 键 词：2型糖尿病 抵当芪桂汤 肠道菌群 代谢组学 大鼠 

分 类 号：R285.5[医药卫生—中药学]