基于肠道菌群驱动磷脂酰胆碱/ApoA-I/HDL亚类代谢探讨脾虚膏脂转输障碍的分子机制

脾虚膏脂转输障碍是动脉粥样硬化性心血管疾病核心病机。课题组前期研究发现脾虚血脂异常人群和模型大鼠均出现肠道菌群组成变化和HDL亚类代谢异常，微生物组学和脂质组学关联分析结果重合提示磷脂酰胆碱代谢异常是肠道菌群失调和脂质代谢紊乱的共同途径，具体机制尚不清楚。新近研究发现磷脂酰胆碱可通过HDL最主要载脂蛋白—ApoA-I调控HDL亚类成熟代谢从而发挥抗AS作用。本课题拟在前期工作基础上，分别以脾失健运膏脂转输障碍人群、无菌小鼠、ApoA-I-/-小鼠为研究对象，从肠道菌群靶向磷脂酰胆碱/ApoA-I/HDL亚类代谢的角度，深入探讨脾失健运—肠道菌群失调—膏脂转输障碍的分子生物学基础，并揭示健脾降脂中药的效应机制，丰富“脾主运化”理论科学内涵，为筛选以肠道菌群驱动磷脂酰胆碱/ApoA-I/HDL亚类代谢为有效靶点的健脾降脂中药及中西医结合防治动脉粥样硬化性心脑血管疾病提供新的研究策略及科学依据。

The disorder of the spleen and Gaozhi transportation and transformation dysfunction are core pathogenesis of atherosclerotic cardiovascular disease. The previous researches of the research group found that the gut microbiota composition changes and HDL subclass metabolism abnormalities occurred in both dyslipidemia population with spleen deficiency and model rats. The association analysis results of microbiome and lipidomics suggested that phosphatidylcholine is a common pathway of gut microbiota imbalance and lipid metabolism disorder, and the specific mechanism remain unknown. Recent studies have found that phosphatidylcholine can regulate the maturation metabolism of HDL subclasses by ApoA-I. This project is conducting the spleen deficiency hyperlipidemia patients, germ-free mouse and apoA-I-/- mouse as the research object, from the perspective of gut microbiota targeting phosphatidylcholine / ApoA-I / HDL subclass metabolism, exploring the molecular biology basis of spleen dysfunction- gut microbiota imbalance- Gaozhi transportation and transformation dysfunction, revealing the effect mechanism of spleen strengthening and lipid-lowering Chinese medicines, and enriching the scientific connotation of " spleen governing transportation and transformation ". These contribute to provide new research strategy and experimental basis for digging the spleen strengthening and lipid-lowering Chinese medicines which is regarding gut microbiota driving phosphatidylcholine / ApoA-I / HDL subclass metabolism as effective targets and preventing and treating atherosclerotic cardiovascular disease from integrative Chinese and Western Medicine.