阿霉素致心肌线粒体损伤的分子机制研究进展  

Research advances in the molecular mechanism of doxorubicin-induced myocardial mitochondrial dysfunction

作　　者：李治邑(综述) 李妙龄(审校) LI Zhiyi;LI Miaoling(Key Laboratory of Medical Electrophysiology of Ministry of Education,Medical Electrophysiology Key Laboratory of Sichuan Prov-ince,Institute of Cardiovascular Research of Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学心血管医学研究所,医学电生理教育部重点实验室,四川省医学电生理重点实验室,泸州646000

出　　处：《西南医科大学学报》2022年第1期77-82,共6页Journal of Southwest Medical University

基　　金：四川省科技厅面上项目(19YYJC1958)。

摘　　要：阿霉素属蒽环类抗肿瘤药,是临床上最有效的抗癌药之一,但其会导致心脏功能的改变和其他器官的损害。由于心肌细胞很难分裂增殖,绝大多数损伤不可逆,很难逆转对心功能的影响。心脏的氧化新陈代谢较快,抗氧化防御水平较低。因此,心脏对自由基引起的损伤很敏感。阿霉素可导致剂量依赖性心肌病和充血性心力衰竭;还可能会发生认知功能的持续性变化(记忆力和注意力丧失以及难以执行多项任务)。阿霉素导致的剂量依赖性心肌病还可导致明显的低血压、心动过速、心脏扩张和心室衰竭。因此,探讨阿霉素诱导心脏毒性作用机制具有重要意义。许多研究试图描述和阐明其心脏毒性作用的机制,尽管有丰富的数据涵盖了抗肿瘤药物阿霉素产生的广泛影响,但确切的机制仍然存在争议。许多研究发现无论是急性还是慢性,线粒体均是阿霉素诱导的氧化应激的主要靶点。本文就阿霉素损伤线粒体导致心脏毒性的分子机制作一综述。Doxorubicin,an anthracycline antitumor drug,is one of the most effective anticancer drugs in clinical practice.How⁃ever,it can cause changes in cardiac function and damage to other organs.Since cardiomyocytes are difficult to divide and proliferate,most injuries are irreversible,and it is difficult to reverse the influence on cardiac function.The heart is involved in a relatively high ox⁃idative metabolism and a relatively low level of antioxidant defense,which makes it sensitive to damage caused by free radicals.Doxoru⁃bicin can lead to dose-dependent cardiomyopathy and congestive heart failure,and even cognitive dysfunction(loss of memory and at⁃tention,difficulty to perform multitasking).And doxorubicin-induced dose-dependent cardiomyopathy can lead to significant hypoten⁃sion,tachycardia,dilatation of the heart,and heart failure.Therefore,it is of great value to investigate the mechanism of action of doxorubicin in cardiotoxicity.Many studies have attempted to describe and elucidate the mechanism of its cardiotoxic effects.Although there have been abundant data covering a wide range of drug-mediated effects,the exact mechanism remains controversial.Many stud⁃ies have found that mitochondria are the main targets of doxorubicin-induced oxidative stress,both in acute and chronic treatments.This article reviews the molecular mechanism of action of doxorubicin in cardiotoxicity through mitochondrial injury.

关 键 词：抗肿瘤药 阿霉素 心脏毒性 线粒体 

分 类 号：R541.9[医药卫生—心血管疾病]