胆汁酸代谢在代谢性心脑血管疾病发生发展中的作用  

Role of bile acid metabolism in occurrence and development of metabolic cardiovascular and cerebrovascular diseases

作　　者：杨婉越 张心怡 于杨 YANG Wanyue;ZHANG Xinyi;YU Yang(School of Laboratory Animal&Shandong Laboratory Animal Center,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan 250117,China;School of Clinical and Basic Medical Sciences,Shandong First Medi-cal University&Shandong Academy of Medical Sciences,Jinan 250117,China)

机构地区：[1]山东第一医科大学(山东省医学科学院)实验动物学院(省实验动物中心),山东济南250117 [2]山东第一医科大学(山东省医学科学院)临床与基础医学院,山东济南250117

出　　处：《中国病理生理杂志》2025年第3期569-576,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金面上项目(No.81970385);山东省自然科学基金面上项目(No.ZR2019MH021)。

摘　　要：胆汁酸作为一种重要的信号分子,通过与法尼酯X受体(farnesoid X receptor,FXR)、Takeda G蛋白偶联受体5(Takeda G protein-coupled receptor 5,TGR5)、鞘氨醇-1-磷酸受体2(sphingosine-1-phosphate receptor 2,S1PR2)等不同的膜受体和核受体结合来调控一系列复杂的代谢网络。研究表明,胆汁酸与多种代谢性心脑血管疾病的发生发展关系密切,如TGR5的激活可减少泡沫细胞的形成和动脉粥样硬化病变;FXR通过抑制甘油三酯合成的基因而调节脂代谢;熊脱氧胆酸有效减少促炎细胞因子,改善外周微循环,降低心力衰竭的风险。本文对胆汁酸的生物合成与代谢、胆汁酸主要受体发挥作用的途径及功能以及胆汁酸与心脑血管疾病发生发展的关系作一综述,为以胆汁酸受体为靶点的机制研究和相关药物研发提供参考。Bile acids,as important signaling molecules,regulate a complex metabolic network by binding to various membrane receptors and nuclear receptors such as farnesoid X receptor(FXR),Takeda G protein-coupled receptor 5(TGR5),and sphingosine-1-phosphate receptor 2(S1PR2).Studies have shown that bile acids are closely related to the occurrence and development of various metabolic cardiovascular and cerebrovascular diseases.For instance,activation of TGR5 can reduce foam cell formation and atherosclerotic lesions,FXR modulates lipid metabolism by inhibiting genes of triglyceride synthesis,and ursodeoxycholic acid effectively reduces pro-inflammatory cytokines,improves peripheral microcirculation and decreases the risk of heart failure.This study provides an overview of the biosynthesis and metabolism of bile acids,the pathways and functions of major bile acid receptors,and the relationship between bile acids and the development of cardiovascular and cerebrovascular diseases,aiming to offer a reference for mechanistic research and drug development targeting bile acid receptors.

关 键 词：胆汁酸 脂质代谢 心血管疾病 脑血管疾病 

分 类 号：R543[医药卫生—心血管疾病] R743[医药卫生—内科学] R363[医药卫生—临床医学]