Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China.
Oxid Med Cell Longev. 2023 Jan 14;2023:9966355. doi: 10.1155/2023/9966355. eCollection 2023.
Cardiotoxicity linked to doxorubicin (DOX) is primarily caused by inflammation, oxidative stress, and apoptosis. The role of tubeimoside I (TBM) in DOX-induced cardiotoxicity remains ambiguous, despite growing evidence that it could reduce inflammation, oxidative stress, and apoptosis in various diseases. This study was designed to investigate the role of TBM in DOX-induced cardiotoxicity and uncover the underlying mechanisms. H9c2 cell line and C57BL/6 mice were used to construct an in vitro and in vivo model of DOX-induced myocardial injury, respectively. We observed that DOX treatment provoked inflammation, oxidative stress, and cardiomyocyte apoptosis, which were significantly alleviated by TBM administration. Mechanistically, TBM attenuated DOX-induced downregulation of sirtuin 3 (SIRT3), and SIRT3 inhibition abrogated the beneficial effects of TBM both in vitro and in vivo. In conclusion, TBM eased inflammation, oxidative stress, and apoptosis in DOX-induced cardiotoxicity by increasing the expression of SIRT3, suggesting that it holds great promise for treating DOX-induced cardiac injury.
多柔比星（DOX）引起的心脏毒性主要是由炎症、氧化应激和细胞凋亡引起的。尽管越来越多的证据表明，它可以减轻各种疾病中的炎症、氧化应激和细胞凋亡，但关于其在 DOX 诱导的心脏毒性中的作用仍存在争议。本研究旨在探讨 TBM 在 DOX 诱导的心脏毒性中的作用，并揭示其潜在机制。使用 H9c2 细胞系和 C57BL/6 小鼠分别构建 DOX 诱导的心肌损伤的体外和体内模型。我们观察到 DOX 处理引发炎症、氧化应激和心肌细胞凋亡，而 TBM 给药可显著缓解这些反应。机制上，TBM 减轻了 DOX 诱导的 SIRT3（沉默调节蛋白 3）下调，而 SIRT3 抑制在体外和体内均消除了 TBM 的有益作用。总之，TBM 通过增加 SIRT3 的表达缓解了 DOX 诱导的心脏毒性中的炎症、氧化应激和细胞凋亡，表明其在治疗 DOX 诱导的心脏损伤方面具有很大的潜力。
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