多柔比星致心脏毒性的可能信号途径  

Signal pathways in doxorubicin-induced cardiotoxicity

作　　者：郭家彬[1] 盛治国[1] 彭双清[1] 

机构地区：[1]军事医学科学院毒物药物研究所国家北京药物安全评价研究中心,北京100850

出　　处：《中国药理学与毒理学杂志》2006年第2期157-160,共4页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目(30572281)~~

摘　　要：多柔比星(Dox)为临床常用的广谱、高效抗肿瘤药物,用于恶性淋巴瘤、实体瘤等多种癌症的治疗。然而,心脏毒性严重限制其临床应用。Dox诱发心脏毒性的作用机制十分复杂,其具体机制至今尚不清楚。Dox可明显上调心脏组织中ROS及TNF-α水平,引起心肌细胞内钙负载及线粒体细胞色素C释放,活化钙信号、p38MAPK、PI3K/Akt等多条信号途径。充分理解这些信号途径在Dox介导心脏毒性过程中的作用对于防治Dox心脏毒性具有重要的指导意义。本文就近年来Dox致心脏毒性的可能信号途径作简要综述。Doxorubicin （Dox） is a broad spectrum and powerful anticancer drug while its use is severely restricted by its cardiotoxicity. Dox can upregulate the expression of reactive oxygen species （ROS） and TNF-α in vitro and in vivo, as well as elevate intracellular calcium level. Several signal pathways including ROS and calcium signaling, cytochrome C, p38 MAPK, PI3K/Akt are involved in the development of doxorubicin-induced cardiotoxicity, which may play a critical role though the precise biochemical mechanism still remains unclear. In this review, we will discuss the potential signal events in doxorubicin-induced cardiotoxicity. We hope it may be of great value in new drug discovery for preventing and curing doxorubicin-induced cardiotoxicity.

关 键 词：多柔比星 心脏毒性 信号途径 细胞凋亡 

分 类 号：R96[医药卫生—药理学]