Doxorubicin (DOX) is a broad spectrum antitumor agent. However, its clinical utility is limited due to the well-known cardiotoxicity. Resveratrol (RSV) has been reported to exert cardioprotective effect in some cardiovascular diseases. In this study, we aimed to determine the effect of RSV on DOX-induced cardiotoxicity, and further explore the underlying mechanism in this process.Male Sprague-Dawley (SD) rats were randomly divided into four groups: CON, DOX, RSV, or DOX+RSV group (10 rats in each group). DOX treatment significantly decreased cardiac function, and increased the release of serum lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) in rat serum. Increased cell death and apoptosis of cardiomyocytes were also observed in DOX group in comparison with CON group. DOX treatment dramatically down-regulated expression of VEGF-B either in vivo or in vitro. In contrast, the combination of RSV and DOX markedly attenuated DOX-induced cardiotoxicity with the up-regulation of VEGF-B. Inhibition of VEGF-B by small interfering RNA (siRNA) abolished the protective effects of RSV on DOX-treated cardiomyocytes.Consequently,our findings indicated that RSV attenuates DOX-induced cardiotoxicity through up-regulation of VEGF-B.

阿霉素（DOX）是一种广谱抗肿瘤药。然而，由于众所周知的心脏毒性，其临床应用受到限制。据报道，白藜芦醇（RSV）在某些心血管疾病中具有心脏保护作用。在这项研究中，我们旨在确定RSV对DOX诱导的心脏毒性的影响，并进一步探索这一过程的潜在机制。雄性Sprague-Dawley（SD）大鼠随机分为4组：CON，DOX，RSV或DOX + RSV组（每组10只大鼠）。DOX处理可显着降低心脏功能，并增加大鼠血清中血清乳酸脱氢酶（LDH）和肌酸激酶同工酶（CK-MB）的释放。与CON组相比，DOX组还观察到细胞死亡和心肌细胞凋亡增加。体内或体外。相反，RSV和DOX的组合显着减弱了DOX诱导的心脏毒性，并上调了VEGF-B的表达。小干扰RNA（siRNA）抑制VEGF-B消除了RSV对DOX处理的心肌细胞的保护作用。因此，我们的发现表明RSV通过上调VEGF-B减轻了DOX诱导的心脏毒性。