摘要
蒽环类化疗药物,如阿霉素是目前许多肿瘤的重要治疗手段之一,但是此类化学药物容易产生心脏毒性。阿霉素治疗引起的急性或长期的心脏毒性受到了临床极大的关注。阿霉素诱导的线粒体功能障碍是阿霉素心脏毒性作用的重要机制,进而诱导活性氧增多、心肌细胞凋亡增加和心脏功能下降。Sirtuins是蛋白质去乙酰化酶,在低能量水平状态下,可被激活并活化相关转录因子,促进能量生成、改善心脏能量代谢。此外,Sirtuins还具有拮抗细胞氧化应激损伤的作用。Sirt1和Sirt3在心肌细胞中高水平表达,通过调节心脏线粒体功能在心力衰竭中起着重要的保护作用。现总结和讨论主要的Sirtuins家族成员Sirt1和Sirt3维持心血管稳态、拮抗阿霉素心脏毒性的作用,探讨Sirt1和Sirt3活化缓解蒽环类化疗药物的心脏毒性而不影响其抗肿瘤活性的可能性。
Anthracycline chemotherapeutic drugs, such as doxorubicin(DOX), are currently one of the most important treatments for most tumors. However, these chemicals are prone to cardiotoxicity. The acute or long-term cardiotoxicity caused by DOX therapy has attracted great attention in clinic. Mitochondrial dysfunction induced by DOX is an important mechanism of DOX cardiotoxicity, which leads to the increase of reactive oxygen species and cardiomyocyte apoptosis and the decrease of cardiac function. Sirtuins, a protein deacetylase family, can be activated at low energy levels and activate related transcription factors to promote energy production and improve heart energy metabolism. In addition, Sirtuins also antagonize oxidative stress injury. Sirt1 and Sirt3 are highly expressed in cardiac myocytes and play an important role in the protection of heart failure by regulating mitochondrial function. In this review, we summarized and discussed the roles of Sirt1 and Sirt3 in maintaining cardiovascular homeostasis and antagonizing Dox-induced cardiotoxicity, and explored the possibility of activating Sirt1 and Sirt3 to alleviate cardiotoxicity of anthracycline chemotherapeutic drugs without affecting their antitumor activity.
作者
吴思思
蒋维
WU Si-Si;JIANG Wei(Research Core Facility,West China Hospital of Sichuan University,Chengdu 610041,China;Molecular Medicine Center,West China Hospital of Sichuan University,Chengdu 610041,China)
出处
《生命科学》
CSCD
北大核心
2019年第7期665-670,共6页
Chinese Bulletin of Life Sciences
基金
国家自然科学基金项目(81700229)
