药物性肝损伤的肝细胞死亡方式及治疗药物研究进展

药物性肝损伤（DILI）是临床常见的肝损伤类型，是严重的药物不良反应之一。细胞死亡是DILI的重要特征，药物可通过诱导内质网应激和激活死亡受体等方式激活凋亡通路，诱导肝细胞凋亡或坏死，诱发肝损伤。除凋亡和坏死外，DILI过程中还伴随着自噬、焦亡和铁死亡。自噬可以清除受损的蛋白质以及细胞器，是肝细胞存活的重要机制，但也可能诱导肝细胞死亡。焦亡和铁死亡是最近发现的细胞死亡方式，其在DILI中的作用尚未完全阐明。阻断肝细胞死亡通路，是治疗DILI的重要手段。水飞蓟素、柚皮素、人参皂苷等可以抑制肝细胞死亡通路，是DILI的潜在治疗药。针对不同细胞死亡方式的机制和特点，研究改善肝细胞死亡的药物对治疗DILI具有重要意义。总结了DILI中肝细胞死亡的机制，并论述了潜在的药物治疗，旨在为DILI的治疗提供参考。

Research advances of hepatocyte death and therapeutic drugs in drug-induced liver injury

Drug-induced liver injury (DILI) is a common clinical type of liver injury and serious adverse drug reaction. Cell death is an important feature of DILI. Drugs can activate the apoptosis pathway by inducing endoplasmic reticulum stress and activating death receptors, induce hepatocyte apoptosis or necrosis, and induce liver injury. In addition to apoptosis and necrosis, the process of DILI is also accompanied by autophagy, pyroptosis and ferroptosis. Autophagy can remove damaged proteins and organelles, and is an important mechanism for liver cell survival, but it may also induce liver cell death. Pyroptosis and ferroptosis are recently discovered cell death methods, and their role in DILI has not yet been fully elucidated. Blocking the hepatocyte death pathway is an important method for the treatment of DILI. Drugs such as silymarin, naringenin, and ginsenosides are potential therapeutic drugs for DILI because they can inhibit hepatocyte death pathways. Therefore, in view of the mechanisms and characteristics of different cell death modes, research on drugs to improve liver cell death is of great significance for the treatment of DILI. This article summarizes the mechanism and effects of liver cell death in DILI, and discusses potential therapeutic drugs, aiming to provide a reference for the treatment of DILI.