基于TMA/FMO3/TMAO通路探讨肝失疏泄对肠道微生物组膏脂转输障碍的影响及机制研究

Discussion on Influence and Mechanism of Dysfunction of Liver Governing Free Flow of Qi on Gut Microbiome and Gaozhi Transportation Dysfunction Based on TMA/FMO3/TMAO pathway

肝失疏泄膏脂转输障碍是血脂异常关键病机,而血脂异常是动脉粥样硬化(AS)重要危险因素。近年来肠道微生物调控脂质代谢成为基础和临床关注的热点,最新研究发现,肠道微生物主要通过调控TMA/FMO3/TMAO通路干预脂质代谢,特别是影响RCT途径。膏脂转输障碍导致RCT受阻,提示肠道微生物改变可能与膏脂转输障碍密切关联。依据中医'肝主疏泄'理论,提出'从肝论治'AS,组成疏肝清脂中药复方,探讨疏肝清脂法对消退、稳定动脉粥样硬化斑块的机制研究。本研究拟以高脂血症模型大鼠为研究对象,以肠道微生物组及其驱动的TMA/FMO3/TMAO通路为切入点,围绕RCT途径,利用宏基因组测序、LC-MS等技术,初步阐明肝失疏泄状态下肠道微生物调控膏脂转输的关键途径、环节及分子机理,并揭示疏肝清脂法的效应机制。丰富'肝主疏泄'理论的科学内涵,并为挖掘以肠道微生物组为有效靶点防治AS相关疾病疏肝降脂中药提供新的研究策略。

Dysfunction of the liver governing free flow of Qi caused lipid transferring disorder is the key pathogenesis of dyslipidemia which is an important risk factor for AS.In recent years,the regulation of lipid metabolism by intestinal microbes has become a focus of basic and clinical attention.Recent studies have found that intestinal microbes mainly interfere with lipid metabolism through regulating the TMA/FMO3/TMAO pathway,especially the RCT pathway.The barrier of ointment and fat transferring is hindered by RCT,which suggests that the change of intestinal microorganism may be closely related to the barrier of ointment and lipid transferring.According to traditional Chinese medicine'liver governing free flow of Qi'theory,it put forward the'treatment from the liver'on AS,making the reducing the lipid through the liver Chinese medicine compound to explore the mechanism of reducing the lipid through the liver method to reduce and stabilize atherosclerotic plaque.This topic was to take hyperlipidemia model rats as the research object,and took the intestinal microorganism group and its driving TMA/FMO3/TMAO pathway as the breakthrough point around the RCT approach.By the use of macrogenome sequencing,LC-MS and other techniques,it preliminary clarified the mechanism of critical path and regulation of lipid transferring process and molecular gut microbial in the dysfunction of the liver governing free flow of Qi,and revealed the effect of reducing the lipid.The rich scientific connotation of'liver governing free flow of Qi'theory and digging the gut microbiome as the the effective target can provide new research methods for reducing the lipid traditional Chinese medicine preventing and treating AS related diseases.