Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats
Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats
复制标题
氧化苦参碱改善多柔比星诱导的大鼠心脏毒性
DOI：
10.1159/000480471
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发表时间：
2017-01-01
影响因子：
--
通讯作者：
Huang, Yongpan
中科院分区：
文献类型：
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作者：
Zhang, Yan-Yan;Yi, Minhan;Huang, Yongpan
背景/目的：阿霉素所致心脏毒性一直是肿瘤学家关注的主要问题，也是限制其临床应用的主要因素。氧化苦参碱具有很强的抗癌、抗纤维化和抗氧化作用。最近，有报道称氧化苦参碱对某些心血管疾病有保护作用。本研究旨在探讨氧化苦参碱对阿霉素诱导的大鼠心脏和H9c2细胞心脏毒性的影响。方法：用商品化试剂盒检测肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)。用商品化试剂盒检测过氧化氢酶(CAT)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)等反映氧化应激的生化指标。荧光显微镜下检测线粒体活性氧(ROS)2‘，7’-二氯二乙酸酯(DCFH-DA)含量。进行组织学分析，观察细胞形态变化，并用商用试剂盒检测细胞凋亡率。Western blotting检测裂解后caspase-3的表达水平。结果：阿霉素治疗可显著增加氧化应激水平，表现为过氧化氢酶、丙二醛、超氧化物歧化酶、谷胱甘肽过氧化物酶和活性氧。阿霉素还可增加心肌组织的病理损伤、心肌ROS水平和丙二醛水平，并诱导心肌组织和H9c2细胞的凋亡。氧化苦参碱可减弱阿霉素的上述作用。结论：氧化苦参碱在体外和体内的研究结果表明，氧化苦参碱可能是一种有希望的抗阿霉素心脏毒性的心脏保护剂，至少部分是通过抑制心肌细胞凋亡和氧化应激来实现的。
Background/Aims: Doxorubicin-induced cardiac toxicity has been a major concern of oncologists and is considered the main restriction on its clinical application. Oxymatrine has shown potent anti-cancer, anti-fibrosis, and anti-oxidative effects. Recently, it has been reported that oxymatrine is protective against some cardiovascular diseases. In this study, we aimed to investigate the effects of oxymatrine on doxorubicin-induced cardiotoxicity in rat hearts and H9c2 cells. Methods: Creatine Kinase - MB (CK-MB) and Lactate Dehydrogenase (LDH) levels were determined using commercial kits. Biochemical indices reflecting oxidative stress, such as catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were also analyzed with commercial kits. Mitochondrial reactive oxygen species (ROS) 2’,7’-dichlorofluorescin diacetate (DCFH-DA) was measured by fluorescence microscopy. Histological analyses were conducted to observe morphological changes, and apoptosis was measured using a commercial kit. Western blots were used to detect the level of expression of cleaved caspase-3. Results: Doxorubicin treatment significantly increased oxidative stress levels, as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione peroxidase and reactive oxygen species. Doxorubicin also increased pathological damage in myocardial tissue, myocardial ROS levels, and malonyldialdehyde levels, and induced apoptosis in myocardial tissues and H9c2 cells. All of these doxorubicin-induced effects were attenuated by oxymatrine. Conclusion: These in vitro and in vivo findings indicate that oxymatrine may be a promising cardioprotective agent against doxorubicin-induced cardiotoxicity, at least in part mediated through oxymatrine’s inhibition of cardiac apoptosis and oxidative stress.