抗结核药物性肝损伤中肝细胞死亡方式研究新进展

Recent advances in research of modes of hepatocyte death in antituberculosis drug-induced liver injury

抗结核药物性肝损伤(anti-tuberculosis drug-induced liver injury,ATB-DILI)是抗结核药物治疗中最常见也是最严重的副作用,给结核病的药物治疗带来了巨大的挑战.异烟肼和利福平等一线抗结核药物在代谢过程中一方面产生多种毒性代谢产物直接造成肝细胞坏死,另一方面产生大量自由基,诱导细胞氧化应激,导致肝细胞凋亡、铁死亡和自噬等程序性死亡.铁死亡是最近发现的细胞死亡方式,其在ATB-DILI中的作用尚未完全阐明.阻断肝细胞死亡通路,是治疗ATBDILI的重要手段.本文针对不同细胞死亡方式的机制和特点进行探讨,以期寻找新的诊断标志物和治疗药物靶点.

Antituberculosis drug-induced liver injury(ATB-DILI)is the most common and most serious side effect of antituberculous drug therapy,which brings great challenges to drug treatment of tuberculosis.Isoniazid and rifampicin as first-line anti-tuberculosis drugs produce a variety of toxic metabolites that directly cause liver cell necrosis,and a large amount of free radicals that induce oxidative stress,leading to programmed death of liver cells such as apoptosis,ferroptosis,and autophagy.Iron death is a recently discovered mode of cell death,and its role in ATBDILI has not been fully elucidated.Blocking the pathway of hepatocyte death is an important means to treat ATB-DILI.In this paper,we discuss the mechanism and characteristics of different cell death modes in order to help identify new diagnostic markers and therapeutic drug targets.