基于肠道菌群及SCFAs/FFAR/肠促胰岛素信号轴探索清胃降浊中药调节糖脂代谢紊乱的机制研究

降糖调脂方经多年临床实践及前期大型临床研究证实，该药具有降糖、调脂、减轻体重、改善胰岛素抵抗的作用，其疗效机制与调节肠道微生态相关，但具体作用途径及靶点仍待阐释。现有研究证实，肠道菌群可通过短链脂肪酸(SCFAs)及其受体游离脂肪酸受体(FFAR)影响肠促胰岛素分泌，从而调节糖脂代谢。综上提出科学假说：肠道菌群失衡是糖脂代谢紊乱的重要发病机制，SCFAs/FFAR/肠促胰岛素是关键信号传导通路；降糖调脂方可基于肠道菌群调节SCFAs/FFAR/肠促胰岛素信号轴，发挥清胃降浊、改善糖脂代谢紊乱功效。本项目拟采用C57BL/6J模型小鼠验证降糖调脂方对糖脂代谢及肠道微生态的影响，进一步利用粪菌移植技术双向阐明降糖调脂方通过调控肠道菌群、SCFAs及其下游受体发挥糖脂同调的疗效机制，旨在为清胃降浊中药调节肠道微生态改善代谢紊乱提供科学依据。

JiangTangTiaoZhi Formula (JTTZF) has been proved in lowering blood glucose, regulating lipids, reducing weight and improving insulin resistance in clinical practice and large-scale clinical trials. Previous study had showed that the mechanism of JTTZF is related to regulating gut microbiota, while the details of action remain to be explored. Researches have confirmed that gut microbiota could regulate glycolipid metabolism by incretin. And the incretin secretion is affected by short-chain fatty acids (SCFAs) and their receptors - free fatty acid receptors (FFAR). So the scientific hypothesis of this project is put forward: the imbalance of gut microbiota is the important pathogenesis of metabolic disorders, SCFAs/FFAR/incretin is the key signal axis for transmission, JTTZF could improve the metabolic disorders by regulating the signal axis of SCFAs/FFAR/incretin via gut microbiota. In this project, C57BL/6J model mice would be used to confirm the efficacy of JTTZF on glycolipid metabolism and gut microbiota, and to further reveal the mechanism of JTTZF is through regulating gut microbiota, SCFAs and their downstream receptors in two-way by fecal microbiota transplantation technology, in order to provide objective basis for regulating gut microbiota and improving metabolic disorders.