法尼醇X受体在治疗胆汁淤积性肝病中的作用机制和药物研究进展  

Research progress on the mechanism of action and drugs of FXR in the treatment of cholestatic liver diseases

作　　者：胡莉 杨伟峰[2] 刘婷[1] 冯伟红[1] 卢晨娜 李春[1] HU Li;YANG Weifeng;LIU Ting;FENG Weihong;LU Chenna;LI Chun(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Medical Experimental Center,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]中国中医科学院医学实验中心,北京100700

出　　处：《中国药物警戒》2024年第10期1184-1191,1199,共9页Chinese Journal of Pharmacovigilance

基　　金：国家重点研发计划(2023YFC3504000);中国中医科学院“使命导向改革”重点专项(CI2023E001TS03);中国中医科学院科技创新工程(CI2021A04402、CI2021A04412、CI2021A04206、CI2021A04807)。

摘　　要：目的综述法尼醇X受体(FXR)在治疗胆汁淤积性肝病中的作用机制及以FXR为靶点的药物研究进展。方法对FXR通过调控胆汁酸的生成、代谢、转运以及肠肝循环等方式改善胆汁淤积的机制进行阐述,对FXR具有的抗炎、抗氧化和抗肝纤维化等作用和机制进行论述,对甾体和非甾体类FXR激动剂和FXR拮抗剂的治疗效果和临床试验进展进行综述。结果与结论胆汁淤积性肝病是以胆汁淤积为主要表现的一组临床常见疾病,其致病机制复杂,也一定程度上决定了用药的复杂性。核受体能调控胆汁酸体内平衡,是目前胆汁淤积治疗药物靶标的研究热点;FXR在保持胆汁酸平衡方面起着至关重要的作用,是一种生理性的胆汁酸核受体,被视为胆汁淤积和相关疾病的主要治疗靶点。随着对FXR研究的不断深入,发现其在胆汁酸稳态、抗炎、抗氧化、抗纤维化方面发挥核心调控作用,FXR激动剂和FXR拮抗剂不断被研发以治疗胆汁淤积性肝病。Objective To review the mechanism of action of farnesoid X receptor(FXR)in the treatment of cholestatic liver disease and the research progress of drugs targeting FXR.Methods The mechanism of FXR in improving cholestasis by regulating bile acid production,metabolism,transport and enterohepatic circulation was expounded.The antiinflammatory,antioxidant and anti-fibrosis effects and mechanisms of FXR were discussed.The therapeutic effects of steroid and non-steroid FXR agonists and FXR antagonists and the progress of clinical trials were reviewed.Results and Conclusion Cholestatic liver disease is a group of common clinical diseases with cholestasis as the main manifestation.Its pathogenic mechanism is complex,which also determines the complexity of medication to a certain extent.Nuclear receptors can regulate the homeostasis of bile acid and are currently a hot research topic for drug targets for the treatment of cholestasis.FXR plays a vital role in maintaining bile acid balance.It is a physiological bile acid nuclear receptor and is regarded as the main therapeutic target for cholestasis and related diseases.With the continuous deepening of research on FXR,it was found that it plays a core regulatory role in regulating bile acid homeostasis,anti-inflammation,anti-oxidation and anti-fibrosis aspects.FXR agonists and FXR antagonists are constantly being developed to treat cholestatic liver diseases.

关 键 词：胆汁淤积性肝病 法尼醇X受体 法尼醇X受体激动剂 法尼醇X受体拮抗剂 

分 类 号：R975.5[医药卫生—药品]