炎症应激条件下特异质药物性肝损伤发生机制研究进展

Research progress in mechanisms of idiosyncratic drug-induced liver injury mediated by inflammatory stress

特异质药物性肝损伤(idiosyncratic drug-induced liver injury, IDILI)是一种发生在少数特殊易感个体,且无法预测的严重药物不良反应。虽然对IDILI发生机制尚未完全了解,但人们提出了多种假说来解释IDILI的作用模式和具体机制,其中炎症应激假说是最重要假说之一。炎症应激条件下,药物与炎症相互作用,可通过诱导炎症细胞因子产生、激活凝血系统、影响代谢物活性、诱导胆汁淤积以及影响线粒体损伤等多种机制介导IDILI的发生。本文将就炎症应激条件下IDILI的主要发生机制和影响因素进行综述,以期为临床前药物开发和药物性肝损伤的基础研究提供参考。

Idiosyncratic drug-induced liver injury(IDILI)is an unpredictable serious adverse drug reaction,which only occurs in a minority of special susceptible individuals.Although the mechanism of IDILI has not been fully understood,several hypotheses have been proposed to explain the action mode and specific mechanism of IDILI.Of these hypotheses,inflammatory stress hypothesis is one of the most important theories.Under the condition of inflammatory stress,drugs interact with inflammation and mediate the occurrence of IDILI through a variety of mechanisms,which can induce the production of inflammatory cytokines,activate coagulation system,affect the activity of metabolites,induce cholestasis,affect mitochondrial damage,and others.This review will summarize the main mechanisms and influencing factors of IDILI mediated by inflammatory stress,in order to provide a reference for preclinical drug development and basic research on drug-induced liver injury.