Pirarubicin (THP), an anthracycline drug, is widely used as a basic therapeutic agent for the treatment of carcinoma and lymphatic malignant tumor. However, it exerts irreversible cardiotoxicity in varying degrees. At present, dexrazoxane (DZR) is the only cardioprotective agent used to treat anthracycline drug-induced cardiotoxicity, but it may reduce the anticancer effect of anthracycline drugs, causing severe granulocytopenia and other adverse reactions. Therefore, it is necessary to discover more effective and less toxic drugs for the treatment of THP-induced cardiotoxicity. The present study aimed to investigate the effects and possible mechanisms of rutin (RUT) against THP-induced cardiomyocyte injury. An in vitro cardiomyocyte injury model of THP-treated murine immortalized cardiomyocytes (HL-1) was used in this study. The results showed that RUT markedly increased the viability of HL-1 cells through protection against THP-induced cardiomyocyte injury. Furthermore, RUT significantly inhibited myocardial oxidative insult by adjusting the levels of intracellular reactive oxygen species (ROS). Our data also indicated that RUT activated JunD signaling pathways, thereby affecting the expression levels of some apoptotic proteins by decreasing miR-125b-1-3p expression level. In addition, intracellular ROS level significantly increased in HL-1 cells treated with THP after miR-125b-1-3p mimic transfection, whereas the expression of JunD was downregulated and that of some apoptotic proteins was upregulated. However, this effect was markedly reversed by RUT. Therefore, we inferred that the protective effect of RUT on THP cardiotoxicity was achieved through regulation of the JunD gene by miR-125b-1-3p. This experiment revealed the protective effect of RUT on THP-induced cardiotoxicity at the non-coding RNA level and provided a theoretical foundation for the application of RUT as a protective agent against THP cardiotoxicity.

中文翻译：

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芦丁通过调节 microRNA-125b-1-3p 介导的 JunD 信号通路来防止吡柔比星诱导的心脏毒性。

吡柔比星（THP）是一种蒽环类药物，被广泛用作治疗癌和淋巴恶性肿瘤的基础治疗剂。然而，它会在不同程度上产生不可逆的心脏毒性。目前，右雷佐生（DZR）是唯一用于治疗蒽环类药物心脏毒性的心脏保护剂，但可能会降低蒽环类药物的抗癌作用，导致严重的粒细胞减少等不良反应。因此，有必要寻找更有效、毒性更小的药物来治疗THP引起的心脏毒性。本研究旨在探讨芦丁（RUT）对THP诱导的心肌细胞损伤的作用和可能的机制。本研究使用了 THP 处理的小鼠永生化心肌细胞 (HL-1) 的体外心肌细胞损伤模型。结果表明，RUT 通过保护 THP 诱导的心肌细胞损伤显着提高了 HL-1 细胞的活力。此外，RUT 通过调节细胞内活性氧 (ROS) 的水平显着抑制心肌氧化损伤。我们的数据还表明，RUT 激活了 JunD 信号通路，从而通过降低 miR-125b-1-3p 表达水平来影响一些凋亡蛋白的表达水平。此外，在转染 miR-125b-1-3p 模拟物后，THP 处理的 HL-1 细胞中细胞内 ROS 水平显着升高，而 JunD 的表达下调，一些凋亡蛋白的表达上调。然而，这种影响被 RUT 显着逆转。所以，我们推断 RUT 对 THP 心脏毒性的保护作用是通过 miR-125b-1-3p 对 JunD 基因的调节来实现的。本实验从非编码RNA水平揭示了RUT对THP诱导的心脏毒性的保护作用，为RUT作为THP心脏毒性保护剂的应用提供了理论基础。