线粒体质量控制在阿霉素心肌损伤中的作用研究进展  

Progress in study of role of mitochondrial quality control in adriamycin myocardial injury

作　　者：刘诗瑶 张梦晓 刘浩 LIU Shi-yao;ZHANG Meng-xiao;LIU Hao(School of Pharmacy,Bengbu Medical College,Anhui Engineering Technology Research Center of Biochemical Pharmaceutical,Bengbu Anhui 233030,China)

机构地区：[1]蚌埠医科大学药学院,安徽省生化药物工程技术研究中心,安徽蚌埠233030

出　　处：《中国药理学通报》2024年第10期1814-1818,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金青年项目(No 82304640);安徽省优秀科研创新团队项目(No 2022AH010084);安徽省生化工程中心科研平台开放课题(No 2023SYKFD06)。

摘　　要：阿霉素(adriamycin/doxorubicin, DOX)是蒽环类抗肿瘤抗生素的代表药,其主要不良反应为心脏毒性,严重影响DOX的临床应用和患者生存质量。线粒体功能受损是DOX心脏毒性的重要病理机制。心脏是高耗能器官,含有丰富的线粒体以支持心肌细胞的能量需要。机体通过线粒体自噬、线粒体融合/裂变、线粒体生物合成以及线粒体未折叠蛋白反应等质量控制机制来维持线粒体稳态。大量研究表明,DOX心脏毒性与破坏心肌细胞内线粒体质量控制系统有关,重建线粒体质量控制稳态能够减轻DOX相关心肌损伤。该文针对心肌线粒体质量控制系统紊乱在DOX心肌损伤中的作用及其潜在机制进行综述,并探讨靶向线粒体质量控制是否为治疗DOX心肌病的潜在策略。Adriamycin/Doxorubicin(DOX)is a representative drug of anthracycline antitumor antibiotics and its main adverse reaction is cardiotoxicity,which seriously affects the clinical application of adriamycin and the quality of life of patients.Mitochondrial dysfunction is an important pathologic mechanism of adriamycin-related cardiotoxicity.The heart is a highly energy-consuming organ,which contains abundant mitochondria to support the energy needs of cardiomyocytes.The body maintains mitochondrial homeostasis through quality control mechanisms such as mitophagy,mitochondrial fusion/fission,mitochondrial biosynthesis and mitochondrial unfolded protein response.Numerous studies have shown that adriamycin cardiotoxicity is associated with the disruption of the mitochondrial quality control system in cardiomyocytes and that reconstruction of mitochondrial quality control homeostasis can mitigate adriamycin-associated myocardial injury.This article addresses the role of disturbances in the myocardial mitochondrial quality control system in DOX myocardial injury and its underlying mechanisms and explores whether targeting mitochondrial quality control is a potential strategy for the treatment of DOX cardiomyopathy.

关 键 词：阿霉素 心肌损伤 线粒体稳态 线粒体融合/裂变 线粒体自噬 线粒体生物发生 线粒体未折叠蛋白反应 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R541.02[医药卫生—基础医学] R542.2R979.1