药物性肝损伤的免疫学机制  

Immunological mechanism of drug-induced liver injury

作　　者：王宇 李爽 刘成海 WANG Yu;LI Shuang;LIU Chenghai(Department of Gastroenterology,Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai 201999,China;Institute of Liver Diseases,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Key Laboratory of Liver and Kidney Diseases of the Ministry of Education,Shanghai Key Laboratory of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海市宝山区中西医结合医院消化科,上海201999 [2]上海中医药大学附属曙光医院肝病研究所,上海201203 [3]教育部肝肾疾病重点实验室,上海市中医临床重点实验室,上海201203

出　　处：《临床肝胆病杂志》2024年第12期2538-2542,共5页Journal of Clinical Hepatology

基　　金：国家自然科学基金(82305099);宝山区卫生健康委优青(育才)计划资助(BSWSYC-2024-07);新一轮(2023—2025年度)宝山区医学重点学(专)科及特色品牌建设项目(BSZK-2023-BZ07)。

摘　　要：药物性肝损伤(DILI)机制复杂,涉及多种途径协同促进并互为因果,其中免疫反应在致病机制中扮演重要角色。在遗传背景因素下,药物活性代谢产物、药物-分子复合物、危险信号分子或可作为DILI发生的免疫反应触发因子,激活药物抗原性超敏反应机制、P-i假说和固有免疫危险信号机制。使肝脏出现固有免疫、适应性免疫级联反应,导致肝脏固有免疫耐受状态失衡,进而造成肝脏组织的免疫炎症性损伤。本文主要阐述DILI的免疫学发生机制,以期为DILI治疗靶点的研发及规避用药不良反应等提供新的思路。Drug-induced liver injury(DILI)has a complex mechanism involving various pathways with a synergistic effect on each other and a causal relationship with each other,among which immune response plays an important role in the pathogenesis of DILI.In the context of genetic background,drug active metabolites,drug-molecule complexes,and danger signal molecules may be used as the trigger factors for immune response in DILI,activating the mechanism of drug antigenic hypersensitivity,P-i hypothesis,and danger signal mechanism in innate immunity.The cascade reaction of innate immunity and adaptive immunity leads to the imbalance of the innate immune tolerance of the liver and thus causes immunoinflammatory injury of liver tissue.This article mainly elaborates on the immunological mechanism of DILI,in order to provide new ideas for the research and development of therapeutic targets for DILI and the methods for avoiding adverse drug reactions.

关 键 词：化学性与药物性肝损伤 免疫 治疗学 

分 类 号：R575[医药卫生—消化系统]