酒精性肝病中基于胆汁酸的调控机制及潜在治疗靶点  

Bile acid-based regulation mechanism and potential therapeutic targets in alcoholic liver disease

作　　者：刘雅丽 柳涛 赵旭[1] 高沿航[1] Liu Yali;Liu Tao;Zhao Xu;Gao Yanhang(Department of Hepatology,the First Hospital of Jilin University,Changchun 130021,Jilin,China)

机构地区：[1]吉林大学第一医院肝胆胰内科,吉林长春130021

出　　处：《中国医学前沿杂志（电子版）》2023年第2期58-64,共7页Chinese Journal of the Frontiers of Medical Science(Electronic Version)

基　　金：国家自然科学基金资助项目(81972265,82170602);吉林省自然科学基金项目(20200201324JC);吉林省卫生人才专项(JLSWSRCZX 2021-079)。

摘　　要：胆汁淤积是酒精性肝病(alcoholic liver disease,ALD)的关键致病因素,不同程度的胆汁淤积发生在ALD的各个阶段。然而,与胆汁淤积有关的病理生理学机制和生物标志物很大程度上是未知的。胆汁淤积主要以胆汁酸(bile acid,BA)转运和平衡紊乱为特点。长期饮酒可以导致人体胆汁酸池大小以及组成异常变化,胆汁酸池的变化也可能影响ALD的严重程度。因此,在ALD的基础和临床研究中,调节胆汁酸代谢及其信号通路被认为是人类ALD的一种潜在治疗策略。本文总结了ALD中基于胆汁酸调节机制的新进展,并提出了ALD各阶段胆汁酸变化不同的新视角,归纳了基于胆汁酸信号通路治疗ALD的潜在靶点,以期为ALD研究和治疗提供新思考。Cholestasis is a key pathogenic factor in alcoholic liver disease(ALD)and variable degrees of cholestasis occur in all stages of ALD.However,the pathophysiologic mechanisms and biomarkers associated with cholestasis are not well characterized.Cholestatic disease is mainly characterized by the disruption of bile acids transport and homeostasis.Chronic alcohol consumption can lead to abnormal changes in the size as well as the composition of the body’s bile acid pool,and changes in the bile acid pool may also affect the severity of alcoholic liver disease.Consequently,in basic and clinical studies,regulation of bile acid metabolism and its signaling pathways has been considered as a potential therapeutic strategy.Modulation of bile acid metabolism or signaling pathways is considered as a potential therapeutic strategy for ALD in humans.In this review,we summarized recent advances in bile acid-based regulatory mechanisms in ALD,provided novel perspectives on the changes in bile acids in various stages of ALD and proposed potential pharmacological therapies for ALD targeting bile acid metabolism and signaling.

关 键 词：胆汁酸稳态 酒精性肝病 肠道菌群 法尼酯X受体 肠肝循环 成纤维细胞生长因子19 

分 类 号：R575[医药卫生—消化系统]