阿霉素是目前最为有效抗肿瘤药物之一，但剂量依赖性的心脏毒性限制其临床应用，目前认为蒽环类药物鳌合铁离子后触发活性氧簇（reactive oxygen species , ROS）大量释放，诱导氧化应激导致心肌损伤。我们前期研究发现阿霉素上调血管紧张素II(Angiotensin II，AngⅡ)表达，而骨髓间充质干细胞（mesenchymal stem cells,MSCs）可以下调AngⅡ表达、修复并减轻阿霉素诱导的心肌损伤，ARB可用来阻断AngⅡ心血管损伤效应，设想在阿霉素给药同时联合给予MSCs和缬沙坦，分别从两个治疗靶点减轻和阻断阿霉素导致的心肌损伤，本课题拟体内外检测阿霉素处理大鼠心肌或心肌细胞的AngⅡ-Nox-ROS通路变化，试图阐明AngⅡ-Nox-ROS通路是诱发阿霉素心肌毒性又一可能的机制，此外，探讨MSCs与ARB联合预防阿霉素心肌损害的可行性并为临床提供实验依据。

Doxorubicin (DOX) are widely used for the treatment of tumors. However, their uses may be limited by progressive cardiotoxicity. Pathomechanism of cardiomyopathy is related to the presence of reactive oxygen species(ROS). Prevention against cardiological adverse effects is very important because of the limited options to reverse them. We previously found that DOX could upregulated Angiotensin II (Ang-II) expression, while repeated intravenous bone marrow mesenchymal stem cells (MSCs) transplantation could improve cardiac function and attenuate collagen remodeling via downregulating Ang-II in DOX treated rats. Valsartan is effective to alleviate various cardiac damages by antagonizing increased Ang-II. Present study proposal is aiming to test the efficacy of combined MSCs and valsartan on preventing and treating DOX-induced cardiac toxicity. Through observing in vitro and in vivo Ang-II-Nox-ROS pathway changes post DOX use in the absence and presence of MSCs and valsartan, we aimed to defining if Ang-II-Nox-ROS pathway might be a novel pathway responsible for DOX-induced cardiac toxicity, and to present evidence of the beneficial effects of combined MSCs and valsartan on preventing and treating DOX-induced cardiac toxicity in an effort to stimulating the future clinical use of this therapy strategy to prevent and alleviate DOX-induced cardiac toxicity.