摘要
阿霉素是目前应用最广泛的抗肿瘤药,但其心脏毒性限制了临床疗效.阿霉素可引起心肌细胞损伤、心脏进行性扩大和不可逆的心肌损伤,最终导致扩张型心肌病及充血性心力衰竭,称为阿霉素心肌病(DIC).DIC的发病机制包括钙处理异常、氧化应激、线粒体破坏、凋亡和自噬等.近期多项研究报道了一种新的调节性细胞死亡——铁死亡参与其发病.现描述铁死亡的主要机制,并总结铁超载、PRMT4、Sirt1/Nrf2/Keap1通路、FUNDC2、METTL14介导的铁死亡在DIC中的作用机制,旨在对DIC病理生理机制有进一步的认识,为DIC治疗及预防提供新的潜在有效靶点.
Abstract
Doxorubicin(DOX)is the most widely used antitumor drug,but its cardiotoxicity limits clinical efficacy.DOX can cause cardiomyocyte loss,progressive cardiac enlargement,and irreversible myocardial injury,ultimately leading to dilated cardiomyopathy and congestive heart failure,called DOX-induced cardiomyopathy(DIC).Several recent studies have reported the involvement of a new type of regulated cell death,ferroptosis,in its pathogenesis.This review describes the major mechanisms of ferroptosis and summarize the mechanisms of iron overload,PRMT4,Sirt1/Nrf2/Keap1 pathway,FUNDC2,and METTL14 mediated ferroptosis in DIC,aiming to gain further insights into the pathophysiological mechanisms of DIC,and to provide a new and potentially effective target for DIC treatment and prevention.
维普
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