杞菊地黄丸对高脂饮食诱导肥胖小鼠肠道黏膜菌群的影响  

Effect of Qi-Ju-Dihuang Pills on intestinal mucosal microbiota of high-fat diet-induced obese mice

作　　者：吴仪 邓娜 周梦思 谭周进 蒋屏[2] WU Yi;DENG Na;ZHOU Mengsi;TAN Zhoujin;JIANG Ping(School of Traditional Chinese Medicine,Hu′nan University of Chinese Medicine,Changsha,Hu′nan 410208,China;不详)

机构地区：[1]湖南中医药大学中医学院,湖南长沙410208 [2]湖南中医药大学第一临床医学院

出　　处：《中国微生态学杂志》2024年第4期373-378,389,共7页Chinese Journal of Microecology

基　　金：湖南省教育厅重点科学项目(2022JJ30440);湖南中医药大学中医学国内一流建设学科(4901-020000200207);中医学湖南省世界一流培育学科。

摘　　要：目的 通过16S rRNA基因测序、网络药理学及分子对接技术探究杞菊地黄丸(QJDHP)对高脂诱导肥胖小鼠肠道黏膜菌群的影响。方法 15只SPF级雄性C57BL/6小鼠被分为正常组(C组,n=5)、模型组(HF组,n=5)及杞菊地黄丸组(QJDHP组,n=5)。造模期间HF组与QJDHP组予高脂饲料喂养4个月,治疗期间QJDHP组灌胃QJDHP水煎液1个月,其余两组灌胃等量无菌水。结束后采集肠道黏膜,采用16S r RNA基因测序分析肠黏膜菌群,gutMGene数据库预测差异菌群代谢产物,网络药理学分析QJDHP干预肥胖的关键靶点,分子对接技术分析关键靶点与差异菌群代谢产物的结合能。结果 NMDS与ANOSIM结果显示三组间具有显著差异(stress=0.057 7;R=0.411,P=0.005)。物种相对丰度分析结果表明,与C组比较,HF组Firmicutes/Bacteroidetes(F/B)值显著升高(t=3.649,P=0.006),与HF组比较,QJDHP组F/B值显著降低。菌群差异分析表明痤疮丙酸杆菌与uncultured bacterium f Muribaculaceae分别为HF组与C组、 HF组与QJDHP组间最具诊断潜力的菌属。IL-6等为QJDHP干预肥胖的关键靶点,获得的5个高活性的差异代谢产物与“IL-6”及“PPARG”均显示了较高的结合能。结论 QJDHP干预抑制了肠道致病菌的增殖,降低了肠道感染风险,降低F/B值,以苯甲酸为代表的5个肠道菌群代谢产物可能是其调节肠道微生态机制的重要分子。Objective To observe the effect of Qi-Ji-Dihuang Pills (QJDHP) intervention on intestinal mucosal microbiota in high-fat diet-induced obese mice using 16S rRNA gene sequencing, network pharmacology, and molecular docking techniques. Methods A total of 15 SPF male C57BL/6 mice were divided into three groups: normal (C group, n=5), model (HF group, n=5) and QJDHP group (n=5). The HF and QJDHP groups underwent four months of high-fat diet, with the latter receiving QJDHP via gavage for one month. Sterile water was administered to the remaining groups. After the intervention, intestinal mucosal samples were collected for 16S rRNA gene sequencing analysis. The gutMGene database was used to predict diverse microbial metabolites. Network pharmacology was used to identify key QJDHP targets in obesity treatment, and molecular docking was used to assess their binding with microbial metabolites. Results NMDS and ANOSIM revealed significant inter-group differences (stress=0.057 7;R=0.411, P=0.005). Comparative species analysis highlighted an increased Firmicutes/Bacteroidetes (F/B) ratio in HF group vs. C group (t=3.649, P=0.006) and a decreased F/B ratio in QJDHP group vs. HF group. Cutibacterium and uncultured bacterium f Muribaculaceae were key genera distinguishing HF group vs. C group and HF group vs. QJDHP group. Key obesity-related targets, including IL-6, were identified for QJDHP intervention. Five metabolites displayed strong binding energies with both "IL-6" and "PPARG". Conclusion Qi-Ji-Dihuang Pills can reduce pathogenic bacteria, lower F/B ratio, regulate energy utilization, and decrease fat storage. Benzoic acid and other gut microbiota metabolites may play a crucial role in Qi-Ji-Dihuang Pills′s intervention on the intestinal microbiota in high-fat-induced obese mice.

关 键 词：杞菊地黄丸 高脂饮食 肠道菌群 代谢产物 分子对接 

分 类 号：R285.5[医药卫生—中药学]