Xin Yan-Fei, Zhou Guo-Liang, Shen Min, Chen Yun-Xiang, Liu Shu-Peng, Chen Guo-Chan, Chen Hao, You Zhen-Qiang, Xuan Yao-Xian
State Key Laboratory of Safety Evaluation for New Drugs, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.
Basic Clin Pharmacol Toxicol. 2007 Dec;101(6):421-6. doi: 10.1111/j.1742-7843.2007.00144.x. Epub 2007 Oct 25.
Doxorubicin is an anthracycline antibiotic agent used in the treatment of a variety of solid and haematopoietic tumours, but its use is limited by formation of metabolites that induce acute and chronic cardiac toxicities. Angelica sinensis has been widely used to treat cardiovascular and cerebrovascular diseases in China. In the present study, we used an in vivo mouse model to explore whether A. sinensis could protect against doxorubicin-induced chronic cardiotoxicity. Male ICR mice were treated with distilled water or water extraction of A. sinensis (15 g/kg, orally) daily for 4 weeks, followed by saline or doxorubicin (15 mg/kg, intravenously) treatments weekly. Cardiotoxicity was assessed by electrocardiograph, antioxidant activity in cardiac tissues, serum levels of creatine kinase, aspartate aminotransferase (AST) and histopathological change in cardiac tissues. A cumulative dose of doxorubicin (60 mg/kg) caused animal death and myocardial injury characterized by increased QT interval and decreased heart rate in electrocardiograph, decrease of heart antioxidant activity, increase of serum AST, as well as myocardial lesions. Pre-treatment with A. sinensis significantly reduced mortality and improved heart performance of the doxorubicin-treated mice as evidenced from normalization of antioxidative activity and serum AST, preventing loss of myofibrils as well as improving arrhythmias and conduction abnormalities. Furthermore, the in vitro cytotoxic study showed that A. sinensis did not compromise the antitumour activity of doxorubicin. These results suggested that A. sinensis elicited a typical cardioprotective effect on doxorubicin-related oxidative stress, and could be a novel adjunct in the combination with doxorubicin chemotherapy.
阿霉素是一种蒽环类抗生素，用于治疗多种实体瘤和造血系统肿瘤，但其使用因诱导急性和慢性心脏毒性的代谢产物的形成而受到限制。当归在中国已被广泛用于治疗心脑血管疾病。在本研究中，我们使用体内小鼠模型来探究当归是否可以预防阿霉素诱导的慢性心脏毒性。雄性ICR小鼠每天用蒸馏水或当归水提取物（15克/千克，口服）处理4周，随后每周用生理盐水或阿霉素（15毫克/千克，静脉注射）处理。通过心电图、心脏组织中的抗氧化活性、血清肌酸激酶水平、天冬氨酸转氨酶（AST）以及心脏组织的组织病理学变化来评估心脏毒性。累积剂量的阿霉素（60毫克/千克）导致动物死亡和心肌损伤，其特征为心电图中QT间期延长和心率降低、心脏抗氧化活性降低、血清AST升高以及心肌病变。当归预处理显著降低了接受阿霉素治疗小鼠的死亡率并改善了心脏功能，这从抗氧化活性和血清AST的正常化、防止肌原纤维丢失以及改善心律失常和传导异常中得到证明。此外，体外细胞毒性研究表明，当归不会损害阿霉素的抗肿瘤活性。这些结果表明，当归对阿霉素相关的氧化应激具有典型的心脏保护作用，并且可能是与阿霉素化疗联合使用中的一种新型辅助药物。
