浙江中医药大学学报2025，Vol.49Issue(6)：661-673,13.DOI:10.16466/j.issn1005-5509.2025.06.001
基于肠道菌群及代谢组学探讨黄连知母汤治疗2型糖尿病的作用机制
Elucidating the Therapeutic Mechanism of Huanglian Zhimu Decoction in Type 2 Diabetes Mellitus Based on Gut Microbiota and Metabolomics
摘要
Abstract
[Objective]To investigate the mechanism of Huanglian Zhimu Decoction in treating type 2 diabetes mellitus(T2DM)rats by 16S ribosomal RNA(16S rRNA)gut microbiota gene sequencing and non-targeted metabolomics.[Methods]Twenty-four GK rats were fed a high-fat diet to induce a T2DM model.After successful modeling,they were divided into T2DM model(MO)group,Huanglian Zhimu Decoction(HL)group and metformin(MET)group.Eight Wistar rats were designated as control(CTRL)group.After 12 weeks of drug intervention,the food intake,water intake,urine volume,body weight and fasting blood glucose of the rats were measured.Biochemical tests were conducted to assess the four lipid profile parameters.Pathological examinations of the liver and colon were observed through hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining.16S rRNA sequencing technology was used for gene sequencing of the fecal microbiota in the rats,and non-targeted metabolomics was performed to detect fecal metabolites.[Results]Huanglian Zhimu Decoction can significantly reduce the fasting blood glucose(P<0.001)and serum levels of total cholesterol(TC),high-density lipoprotein(HDL)and low-density lipoprotein(LDL)in T2DM rats(P<0.05,P<0.01).It also alleviates hepatic steatosis and inflammatory cell infiltration in the liver tissue of T2DM rats induced by high-fat diet,and the synthesis of glycogen increased.Additionally,it repairs the intestinal barrier damage in the colonic tissue to a certain extent and reduce the infiltration of inflammatory cells.16S rRNA gene sequencing analysis revealed that Huanglian Zhimu Decoction can ameliorate intestinal microbiota disruption by reducing the ratio of Firmicutes to Bacteroidota(F/B)at the phylum level,down-regulating the abundance of harmful bacterial genera such as Allobaculum,Colidextribacter,Oscillibacter and Dorea,and up-regulating the abundance of beneficial bacterial genera including Prevotella_9 and Akkermansia muciniphila.Fecal metabolomics analysis indicated that Huanglian Zhimu Decoction improved abnormalities in primary bile acid metabolism and linoleic acid metabolism.[Conclusion]Huanglian Zhimu Decoction can reduce the fasting blood glucose and blood lipid levels in T2DM rats,and its mechanism of action may be related to regulating the structure of intestinal flora and influencing the metabolic pathways of primary bile acids and linoleic acid.These findings provide basis for further studying the mechanism of action of Huanglian Zhimu Decoction.关键词
黄连知母汤/2型糖尿病/肠道菌群/代谢组学/GK大鼠/F/B比值/普雷沃菌属/嗜黏蛋白阿克曼菌Key words
Huanglian Zhimu Decoction/type 2 diabetes mellitus/gut microbiota/metabolomics/GK rats/F/B ratio/Prevotella/Akkermansia muciniphila分类
医药卫生引用本文复制引用
王磊,涂文玲,曹灵勇..基于肠道菌群及代谢组学探讨黄连知母汤治疗2型糖尿病的作用机制[J].浙江中医药大学学报,2025,49(6):661-673,13.基金项目
国家自然科学基金项目(82104803) （82104803）
浙江省自然科学基金项目(ZCLY24H2702) National Natural Science Foundation Project(82104803) （ZCLY24H2702）
Zhejiang Provincial Natural Science Foundation Project(ZCLY24H2702) （ZCLY24H2702）
