蒽环类药物相关心脏毒性的发病机制

The pathogenesis of cardiotoxicity associated with anthracyclines treatment

蒽环类药物广泛用于治疗各种实体肿瘤、血液系统恶性肿瘤,并常与其他化疗药物联合使用。但由于蒽环类药物对机体正常组织的毒性作用,特别是心脏毒性,使其临床应用受到了极大的限制。关于蒽环类药物相关心脏毒性发病机制的研究目前尚不十分明确,传统学说认为其主要与氧化应激、钙超载、拓扑异构酶有关,最新研究发现某些信号通路,如神经调节蛋白生长因子1(neuregulin-1,NRG-1)/Erb B信号通路、腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)信号通路有关,某些受体包括β肾上腺素受体(β-adrenergic receptor,βAR)和Toll样受体(Toll-like receptors,TLRs)等也参与其中。本文结合传统观点及最新研究进展对其发病机制进行综述,以期为临床预防和治疗蒽环类药物引起的心脏损伤提供新的思路。

Anthracyclines are the most potent and widely used anti-neoplastic agents for the treatment of solid tumors and hematological malignancies,and often used with other chemotherapy drugs together.However,their clinical application is greatly restricted as their severe cardiotoxic side effects.The study on the pathogenesis of cardiotoxicity associated with anthracyclines treatment is not very clear.Anthracycline cardiotoxicity has been originally ascribed to the oxidative stress,calcium overload and topoisomerase.New players such as some signal pathways including neuregulin-1/ErbB,AMP-activated protein kinase(AMPK),and some receptors includingβ-adrenergic receptor(βAR)and Toll-like receptors(TLRs)have been considered to be involved recently.This review summarizes the pathogenesis of cardiotoxicity associated with anthracyclines treatment,and provide suggestions for clinical prevention and treatment of cardiac injuries caused by anthracyclotic agents.