胆汁酸代谢调节胆汁淤积性肝病的作用机制及药物研发  

Mechanism of action of bile acid metabolism in regulating cholestatic liver disease and the research and development of drugs

作　　者：李静 郑葵阳 张蓓蓓 LI Jing;ZHENG Kuiyang;ZHANG Beibei(Department of Pathogenic Biology and Immunology,Xuzhou Medical University/Laboratory of Infection and Immunology,Xuzhou Medical University/Jiangsu Key Laboratory of Immunology and Metabolism,Xuzhou,Jiangsu 221004,China)

机构地区：[1]徐州医科大学病原生物学与免疫学教研室,徐州医科大学感染与免疫实验室,江苏省免疫与代谢重点实验室,江苏徐州221004

出　　处：《临床肝胆病杂志》2021年第10期2482-2487,共6页Journal of Clinical Hepatology

基　　金：江苏省自然科学基金项目(BK20201011);江苏省高校自然科学研究项目一项(20KJB310011);江苏省博士后基金项目(RC7062005);研究生科研创新计划(KYCX20-2468)。

摘　　要：胆汁酸是胆固醇代谢的终末产物,包括初级胆汁酸和次级胆汁酸两大类,其可通过作用于胆汁酸核受体和膜受体影响物质吸收和调节免疫应答、糖、脂和能量代谢、肠道菌群稳态。胆汁淤积性肝病(CLD)是由胆汁淤积导致肝胆系统病变引起的肝脏疾病,该病的发生首先表现为肝细胞和/或胆管损伤,继而进一步引起胆汁合成、分泌以及排泄障碍。随着研究的深入,胆汁酸在CLD中的作用及机制已逐步得到阐明,并已有针对胆汁酸作用位点的靶向药物的研发。重点叙述胆汁酸代谢在CLD中的作用及机制,并归纳基于胆汁酸代谢治疗CLD的药物研发情况,为今后CLD的预防及治疗的研究提供参考。Bile acids are the end products of cholesterol metabolism and are classified as primary bile acids and secondary bile acids.They can promote nutrition absorption and regulate immune response,glucose/lipid/energy metabolism,and microbiota homeostasis by acting on bile acid nuclear receptors and membrane receptors.Cholestatic liver disease(CLD)is a type of liver disease caused by abnormalities of the hepatobiliary system due to cholestasis,with the initial manifestations of hepatocyte and/or bile duct injury,which further leads to abnormal bile acid synthesis,secretion,and excretion.In-depth studies have gradually revealed the role and mechanism of bile acids in CLD,and drugs targeting the action sites of bile acids are under research and development.This article elaborates on the role and mechanism of bile acid metabolism in CLDand summarizes the research and development of drugs for CLD treatment based on bile acid metabolism,so as to provide a reference for future research on the prevention and treatment of CLD.

关 键 词：胆汁淤积 胆酸类 病理过程 药物设计 

分 类 号：R575.2[医药卫生—消化系统]