Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, 182 Tianmushan Road, Hangzhou, 310013, Zhejiang, China.
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
BMC Complement Altern Med. 2019 Nov 19;19(1):317. doi: 10.1186/s12906-019-2686-2.
Doxorubicin (DOX) is a chemotherapy drug for malignant tumors. The clinical application of DOX is limited due to its dosage relative cardiotoxicity. Oxidative damage and cardiac inflammation appear to be involved in DOX-related cardiotoxicity. Shenmai injection (SMI), which mainly consists of Panax ginsengC.A.Mey.and Ophiopogon japonicus (Thunb.) Ker Gawl, is widely used for the treatment of atherosclerotic coronary heart disease and viral myocarditis in China. In this study, we investigated the protective effect of Shenmai injection on doxorubicin-induced acute cardiac injury via the regulation of inflammatory mediators.
Male ICR mice were randomly divided into seven groups: control, DOX (10 mg/kg), SMI (5 g/kg), DOX with pretreatment with SMI (0.5 g/kg, 1.5 g/kg or 5 g/kg) and DOX with post-treatment with SMI (5 g/kg). Forty-eight hours after the last DOX administration, all mice were anesthetized for ultrasound echocardiography. Then, serum was collected for biochemical and inflammatory cytokine detection, and heart tissue was collected for histological and Western blot detection.
A cumulative dose of DOX (10 mg/kg) induced acute cardiotoxicity in mice manifested by altered echocardiographic outcome, and increased tumor necrosis factor, interleukin 6 (IL-6), monocyte chemotactic protein 1, interferon-γ, and serum AST and LDH levels, as well as cardiac cytoplasmic vacuolation and myofibrillar disarrangement. DOX also caused the increase in the expression of IKK-α and iNOS and produced a large amount of NO, resulting in the accumulation of nitrotyrosine in the heart tissue. Pretreatment with SMI elicited a dose-dependent cardioprotective effect in DOX-dosed mice as evidenced by the normalization of serum inflammatory mediators, as well as improve dcardiac function and myofibril disarrangement.
SMI could recover inflammatory cytokine levels and suppress the expression of IKK-α and iNOS in vivo, which was increased by DOX. Overall, there was evidence that SMI could ameliorate DOX-induced cardiotoxicity by inhibiting inflammation and recovering heart dysfunction.
阿霉素（DOX）是一种用于恶性肿瘤的化疗药物。由于其剂量相关的心脏毒性，DOX 的临床应用受到限制。氧化损伤和心脏炎症似乎与 DOX 相关的心脏毒性有关。参麦注射液（SMI）主要由人参和麦冬组成，在中国广泛用于治疗动脉粥样硬化性冠心病和病毒性心肌炎。在这项研究中，我们通过调节炎症介质来研究参麦注射液对阿霉素诱导的急性心脏损伤的保护作用。
雄性 ICR 小鼠随机分为七组：对照组、DOX（10mg/kg）、SMI（5g/kg）、DOX 预处理 SMI（0.5g/kg、1.5g/kg 或 5g/kg）和 DOX 后处理 SMI（5g/kg）。DOX 给药后 48 小时，所有小鼠均进行超声心动图检查。然后，收集血清进行生化和炎症细胞因子检测，并收集心脏组织进行组织学和 Western blot 检测。
累积剂量的 DOX（10mg/kg）在小鼠中引起急性心脏毒性，表现为超声心动图结果改变，肿瘤坏死因子、白细胞介素 6（IL-6）、单核细胞趋化蛋白 1、干扰素-γ和血清 AST 和 LDH 水平升高，以及心脏细胞质空泡化和肌原纤维排列紊乱。DOX 还导致 IKK-α 和 iNOS 的表达增加，并产生大量的 NO，导致心脏组织中硝基酪氨酸的积累。SMI 预处理在 DOX 给药的小鼠中表现出剂量依赖性的心脏保护作用，表现在血清炎症介质的正常化，以及改善的心脏功能和肌原纤维排列紊乱。
SMI 可以恢复体内 DOX 升高的炎症细胞因子水平，并抑制 IKK-α 和 iNOS 的表达。总的来说，有证据表明 SMI 可以通过抑制炎症和恢复心脏功能来改善 DOX 诱导的心脏毒性。
