中药防治阿霉素心脏毒性的作用机制及应用

蒽环类抗肿瘤药阿霉素(adriamycin,ADR)抗肿瘤谱广,已被广泛用于急性淋巴细胞白血病、肺癌、乳腺癌等多种类型肿瘤病证的治疗,疗效显著。但ADR呈现出广泛严重的机体毒性,尤其是其在心肌细胞中累积,使得心肌组织更易受到ADR的损害,并呈剂量依赖的不可逆损伤特性,极大地限制了ADR用于临床治疗的使用剂量,并增加了癌症治疗幸存者心血管疾病的发病率和死亡率。目前认为,ADR的心肌毒性是多种因素共同作用的结果,如活性氧自由基的大量生成、钙过载、线粒体损伤、凋亡和自噬等。这些因素之间相互联系、互为因果,形成恶性循环网络,共同促进其心脏毒性的发展。迄今为止,没有一种单一的药物或是方法可以特别有效地预防ADR引起的心脏毒性而不降低其抗癌疗效。因此,寻找一种更安全有效的拮抗ADR心脏毒性的药物或方法仍是一个严峻的挑战。中药具有多靶点多效应的作用特性,可通过抗氧化应激,清除自由基,调节钙的代谢,保护线粒体损伤和拮抗心肌细胞凋亡等多种方式发挥综合作用。近年来,关于中药及其效应成分保护或减轻ADR引起心脏毒性的研究报道较多,作用机制研究也取得了长足的进步。因此,本文就近10年来中药在防治ADR心脏毒性方面的应用及作用机制研究进行归纳总结,以为临床中药配伍ADR更安全合理的使用提供一定的参考。

Application and Mechanism of Traditional Chinese Medicine in Prevention and Treatment of Adriamycin-induced Cardiotoxicity

Adriamycin (ADR), an anthracycline drug, is widely used and clearly effective in the treatment of acute lymphoblastic leukemia, lung cancer, breast cancer and other diseases, with a broad anti-tumor spectrum. However, ADR shows extensive and severe toxicity. Especially, the accumulation of cardiac myocytes causes myocardial tissues more vulnerable to ADR, demonstrating an irreversible dose-dependent injury. Thus, the dosage of ADR is enormously limited in clinical applications. Meanwhile, the incidence and mortality of cardiovascular diseases in cancer survivors has been increased. It is believed that adriamycin-induced cardiotoxicity is the result of a variety of factors, such as the mass formation of reactive oxygen free radicals, calcium overload, mitochondrial damage, apoptosis and autophagy. These factors are interrelated and mutually causative, forming a vicious circulating network to jointly promote the development of their cardiotoxicity. So far, no single drug or method has been particularly effective in preventing adriamycin-induced cardiotoxicity, without reducing its anticancer efficacy. Therefore, it is still a severe challenge to find a safer and more effective drug or method to fight against adriamycin-induced cardiotoxicity. Many traditional Chinese medicines(TCM) with the characteristics of multiple targets and multiple effects, can antagonize adriamycin-induced cardiotoxicity by antioxidant stress, scavenging free radicals, regulation of calcium metabolism, protection of mitochondrial damage and antagonism of myocardial cell apoptosis. In recent years, lots of researches on TCM and their effective components in protection and reduction of adriamycin-induced cardiotoxicity have been reported and great progresses have been made for the researches on mechanism of action. This article reviews the research progresses on the application and mechanism of TCM and the effective components in the prevention and treatment of adriamycin-induced cardiotoxicity in the last ten years, in order to provide certain reference for safer and more reasonable clinical use of adriamycin combined with TCM.