铁死亡与急性肝损伤研究进展

Progress of relationship between ferroptosis and acute liver injury

目的 总结铁死亡在急性肝损伤中的作用机制及研究进展。方法 检索近几年来国内外关于铁死亡与急性肝损伤相关研究的文献并进行综述。结果 铁死亡是一种铁依赖性的细胞死亡形式。谷胱甘肽过氧化物酶4对脂质过氧化修复活性的丧失,氧化还原活性铁的存在和含多不饱和脂肪酸的磷脂氧化被认为是铁死亡的主要特征。目前铁死亡基因调控研究涉及常见肝脏疾病,包括药物诱导性肝损伤、肝细胞癌、肝纤维化、肝缺血再灌注损伤、肝功能衰竭、非酒精性脂肪肝等。基于铁死亡与急性肝损伤的研究结果之间存在高度相关性,未来利用靶向铁死亡的药物治疗,可为急性肝损伤患者提供个体化治疗方案。结论 铁死亡调控许多细胞生物过程以及其他下游效应,其异常表达从各个方面影响肝损伤的发生与发展。深入探究铁死亡基因调控在急性肝损伤中的作用,对寻找治疗急性肝功能损伤的新靶点具有重要意义。

Objective To summarize the mechanism and research progress of ferroptosis in acute liver injury.Method The domestic and foreign literatures related of ferroptosis and acute liver injury were searched and reviewed.Results Ferroptosis was a newly identified form of iron-dependent cell death.The loss of lipid peroxidation repair activity of glutathione peroxidase 4,the presence of redox active iron and the oxidation of phospholipids containing polyunsaturated fatty acids were considered to be distinctive features of ferroptosis.At present,the research on the regulation of ferroptosis genes involved common liver diseases,including drug-induced liver injury,hepatocellular carcinoma,liver fibrosis,liver ischemia-reperfusion injury,liver failure,nonalcoholic fatty liver and so on.Based on the high correlation between ferroptosis and acute liver injury,chemical therapy targeting ferroptosis could provide individualized treatment for patients with acute liver injury in the future.Conclusions The ferroptosis plays a critical role in governing various cellular processes and downstream effects.Its aberrant expression contributes to the development and advancement of acute liver injury through diverse mechanisms.Thoroughly exploring the involvement of the ferroptosis in acute liver injury is of utmost significance,as it holds the potential to unveil novel therapeutic targets for effective management of acute liver injury.