基于TMA/FMO3/TMAO信号通路探讨清脂通脉颗粒对膏脂转输障碍大鼠肠道微生态的调控机制  

Study on Regulation Mechanism of Qingzhi Tongmai Granules on Intestinal Microecology in Rats with Obstruction of Plaster Transfer Based on TMA/FMO3/TMAO Signaling Pathway

作　　者：张欢[1] 周莹莹[2] 于游[1] 郑一[1] 胡楠 赵宏月[1] 郭鹤[1] 于睿[1] ZHANG Huan;ZHOU Yingying;YU you;ZHENG Yi;HU Nan;ZHAO Hongyue;GUO He;YU Rui(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;Shenyang Children’s Hospital,Shenyang 110847,Liaoning,China;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]沈阳市儿童医院,辽宁沈阳110032 [3]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《中华中医药学刊》2020年第10期134-137,共4页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金(81674078);辽宁省自然科学基金(201602501);辽宁省“兴辽英才计划”项目(XLYC1802004);辽宁省教育厅科学技术研究项目(L201948)。

摘　　要：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(athrosclerosis,AS)重要危险因素。研究表明,肠道微生物组能调控胆固醇胆固醇逆转运(RCT)导致的动脉炎性反应,激活胆固醇7α-羟化酶(CYP7A1)调节脂质代谢,改善动脉粥样硬化(AS),但机制不清。前期工作发现,肠道微生物组可能是通过调控TMA/FMO3/TMAO通路在脂质代谢致AS中发挥促进作用,项目拟从TMA/FMO3/TMAO通路为切入点,制作病证结合的模型大鼠,研究肠道微生物组对膏脂转输障碍致AS的保护作用及对TMA/FMO3/TMAO通路的影响,阐明TMA/FMO3/TMAO通路及其调控的下游分子在肠道微生物组对膏脂转输障碍致AS的作用机制,通过研究为寻找增强内源性TMA/FMO3/TMAO通路治疗靶点,来重建肠道微生物组稳态防治AS的疏肝清脂中药提供新的研究策略。Dysfunction of the liver governing free flow of Qi caused lipid transfer disorder is the key pathogenesis of dyslipidemia,dyslipidemia is an important risk factorfor AS.Studies have shown that intestinal microorganisms can regulate the inflammatory response induced by reversed cholesterol cholesterol transport(RCT),activate cholesterol 7alpha hydroxylase(CYP7A1)to regulate lipid metabolism andimprove atherosclerosis(AS),but the mechanism is unclear.Our previous work hasfound that intestinal microbiology may play a role in promoting lipidmetabolism-induced AS by regulating TMA/FMO3/TMAO pathway.This project aims to make a model rat with combination of disease and syndrome from TMA/FMO3/TMAOpathway,to study the protective effect of intestinal microbiology on AS caused bypaste-lipid transport barrier and its effect on TMA/FMO3/TMAO pathway,and toelucidate TMA/FMO3/TMAO pathway and its effect.The mechanism of downstream regulated molecules in intestinal microbiology on AS caused by plaster fattransporting disorder provides a new research strategy for searching for therapeutic targets to enhance endogenous TMA/FMO3/TMAO pathway and reconstruct the homeostasis of traditional Chinese medicine of soothing liver and clearing lipid for preventing AS in intestinal microbiology group.

关 键 词：肝失疏泄 膏脂转输障碍 肠道微生物组 TMA/FMO3/TMAO通路 

分 类 号：R285.5[医药卫生—中药学]