[關(guān)鍵詞]
[摘要]
藥物性肝損傷(DILI)是臨床常見的肝損傷類型,是嚴(yán)重的藥物不良反應(yīng)之一。細(xì)胞死亡是DILI的重要特征,藥物可通過誘導(dǎo)內(nèi)質(zhì)網(wǎng)應(yīng)激和激活死亡受體等方式激活凋亡通路,誘導(dǎo)肝細(xì)胞凋亡或壞死,誘發(fā)肝損傷。除凋亡和壞死外,DILI過程中還伴隨著自噬、焦亡和鐵死亡。自噬可以清除受損的蛋白質(zhì)以及細(xì)胞器,是肝細(xì)胞存活的重要機(jī)制,但也可能誘導(dǎo)肝細(xì)胞死亡。焦亡和鐵死亡是最近發(fā)現(xiàn)的細(xì)胞死亡方式,其在DILI中的作用尚未完全闡明。阻斷肝細(xì)胞死亡通路,是治療DILI的重要手段。水飛薊素、柚皮素、人參皂苷等可以抑制肝細(xì)胞死亡通路,是DILI的潛在治療藥。針對不同細(xì)胞死亡方式的機(jī)制和特點(diǎn),研究改善肝細(xì)胞死亡的藥物對治療DILI具有重要意義??偨Y(jié)了DILI中肝細(xì)胞死亡的機(jī)制,并論述了潛在的藥物治療,旨在為DILI的治療提供參考。
[Key word]
[Abstract]
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.
[中圖分類號]
R969.3
[基金項(xiàng)目]
國家自然科學(xué)基金面上項(xiàng)目(81773995,81973562);國家重大新藥創(chuàng)制專項(xiàng)(2015ZX09501004-002-004)