抗结核药物性肝损伤分子机制研究进展

Research progress in the molecular mechanism of anti-tuberculosis drug-induced liver injury

结核病是全球公共卫生问题,抗结核药物所伴随的肝损伤严重影响预后,因此阐明抗结核药物性肝损伤的分子机制尤为重要。抗结核药物诱导的肝损伤分子机制纷繁复杂,本文将着重从当前最新研究热点进行综述,研究表明抗结核药物性肝损伤(ATB-DILI)与脂质过氧化、铁死亡、表观遗传修饰、代谢组学、环状RNA密切相关。脂质过氧化和铁死亡介导ATB-DILI发生的信号通路与谷胱甘肽代谢有关;表观遗传修饰通过DNA甲基化(和去甲基化)、组蛋白修饰和非编码RNA参与ATB-DILI的致病机制;靶向与非靶向代谢组学在阐明抗结核药物的毒性机制方面具有重要贡献;环状RNA在转录翻译水平参与调控ATBDILI的发生发展。本文旨在阐明抗结核药物性肝损伤分子机制的最新研究进展,以期为后续研究提供理论参考依据及新的研究方向。

Tuberculosis is a global public health problem,and the liver injury associated with anti-tuberculosis drugs seriously affects the prognosis,so it is crucial to clarify the molecular mechanism of anti-tuberculosis drug-induced liver injury(ATB-DILI).The molecular mechanism of ATB-DILI is complex.This article will focus on the review of the latest research hotspots,research shows that ATB-DILI is closely related to lipid peroxidation,ferroptosis,epigenetic modification,metabolomics,and circular RNA;the signaling pathway of ATB-DILI mediated by lipid peroxidation and ferroptosis is related to glutathione metabolism;epigenetic modification is involved in the pathogenesis of ATB-DILI through DNA methylation(and demethylation),histone modification and non-coding RNA;targeted and non-targeted metabolomics play an important role in clarifying the toxicity mechanism of anti-tuberculosis drugs;circular RNA participates in regulating the onset and development of ATB-DILI at the level of transcription and translation.This article is intended to clarify the latest research progress in the molecular mechanism of ATB-DILI,with a view to providing theoretical basis and new research directions for follow-up research.