Salidroside Improves Doxorubicin-induced Cardiac Dysfunction by Suppression of Excessive Oxidative Stress and Cardiomyocyte Apoptosis
Salidroside Improves Doxorubicin-induced Cardiac Dysfunction by Suppression of Excessive Oxidative Stress and Cardiomyocyte Apoptosis
复制标题
红景天苷通过抑制过度氧化应激和心肌细胞凋亡来改善阿霉素诱导的心脏功能障碍
DOI：
10.1097/fjc.0000000000000009
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发表时间：
2013-12-01
影响因子：
3
通讯作者：
Jiang, Wei
中科院分区：
文献类型：
--
作者：
Wang, Xu-Lei;Wang, Xue;Jiang, Wei
摘要：阿霉素（DOX）是一种有效的抗肿瘤药物。然而，其临床应用因心脏毒性而受到限制。红景天苷 (SLD) 具有很强的抗氧化和细胞保护作用，在开发针对心脏病氧化损伤的抗氧化疗法方面特别令人感兴趣。目前，SLD 对 DOX 引起的心脏毒性的保护作用和潜在机制仍不清楚。在本研究中，我们揭示了 SLD 保护中涉及的抗氧化机制和 Bcl2 依赖性生存信号。我们观察到，DOX 暴露会导致小鼠死亡率升高、体重减轻和心脏功能障碍，增加乳酸脱氢酶渗漏和心肌细胞凋亡，但会降低心脏组织和培养的 H9c2 细胞的细胞活力和大小，而 SLD 补充剂可有效拮抗这些现象。我们进一步观察到，SLD 显着降低细胞间氧化应激水平，部分是通过抑制 NOX1 表达并增强内源性抗氧化酶、过氧化氢酶和锰超氧化物歧化酶的表达和活性。此外，SLD 治疗上调抗凋亡 Bcl2，下调促凋亡 Bax，并抑制 Bcl2/Bax 和 caspase-3 活性的下游通路。我们的结果表明，SLD 通过抑制过度氧化应激和激活 Bcl2 介导的生存信号通路，有效保护心肌细胞免受 DOX 诱导的心脏毒性。
Abstract: Doxorubicin (DOX) is a potent available antitumor drug; however, its clinical use is limited by the cardiotoxicity. Salidroside (SLD), with strong antioxidative and cytoprotective actions, is of particular interest in the development of antioxidative therapies for oxidative injury in cardiac diseases. Now, the protection and underlying mechanisms of SLD against DOX-induced cardiotoxicity are still unknown. In the present study, we revealed both antioxidative mechanism and Bcl2-dependent survival signaling involved in SLD's protection. We observed that DOX exposure induced mortality elevation, body weight loss, and cardiac dysfunction in mice, increased lactate dehydrogenase leakage and cardiomyocyte apoptosis, but decreased cell viability and size in cardiac tissues and cultured H9c2 cells, respectively, which were effectively antagonized by SLD supplement. We further observed that SLD significantly reduced the intercellular oxidative stress level, partly by inhibiting NOX1 expression and augmenting the expression and activities of the endogenous antioxidative enzymes, catalase, and manganese superoxide dismutase. In addition, SLD treatment upregulated the antiapoptotic Bcl2 and downregulated the proapoptotic Bax and inhibited a downstream pathway of Bcl2/Bax and caspase-3 activity. Our results indicated that SLD effectively protected the cardiomyocytes against DOX-induced cardiotoxicity by suppressing the excessive oxidative stress and activating a Bcl2-mediated survival signaling pathway.