Asiatic Acid Protects against Doxorubicin-Induced Cardiotoxicity in Mice
Asiatic Acid Protects against Doxorubicin-Induced Cardiotoxicity in Mice
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积雪草酸可预防阿霉素引起的小鼠心脏毒性
DOI：
10.1155/2020/5347204
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发表时间：
2020-05-16
影响因子：
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通讯作者：
Shen, Bin
中科院分区：
文献类型：
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作者：
Hu, Xiaoping;Li, Baijun;Shen, Bin
多柔比星（DOX）的使用可导致心功能下降和难治性心肌病。目前，还没有有效的方法来预防dox相关的心脏并发症。据报道，亚细亚酸（AA）对几种心血管疾病具有保护作用。然而，AA是否能减轻dox相关的心脏损伤尚不清楚。小鼠腹腔注射DOX （15 mg/kg）模拟急性心脏损伤，并给予AA （10 mg/kg或30 mg/kg）保护2周。我们的研究数据发现，注射DOX后，aa处理的小鼠心脏损伤减轻，心功能改善。AA还能抑制dox处理小鼠的心肌氧化损伤和细胞凋亡，而不影响心脏炎症。在体外实验中，AA还对dox挑战的心肌细胞提供保护，提高细胞活力，抑制细胞内活性氧（ROS）。信号通路检测表明，AA在体内和体外均激活了AKT信号通路。此外，我们发现随着AKT失活，AA在心脏中失去了保护作用。综上所述，我们的研究结果发现，AA可以通过激活AKT信号通路来减弱dox诱导的心肌氧化应激和细胞凋亡。
The use of doxorubicin (DOX) can result in depression of cardiac function and refractory cardiomyopathy. Currently, there are no effective approaches to prevent DOX-related cardiac complications. Asiatic acid (AA) has been reported to provide cardioprotection against several cardiovascular diseases. However, whether AA could attenuate DOX-related cardiac injury remains unclear. DOX (15 mg/kg) was injected intraperitoneally into the mice to mimic acute cardiac injury, and the mice were given AA (10 mg/kg or 30 mg/kg) for 2 weeks for protection. The data in our study found that AA-treated mice exhibited attenuated cardiac injury and improved cardiac function in response to DOX injection. AA also suppressed myocardial oxidative damage and apoptosis without affecting cardiac inflammation in DOX-treated mice. AA also provided protection in DOX-challenged cardiomyocytes, improved cell viability, and suppressed intracellular reactive oxygen species (ROS) in vitro. Detection of signaling pathways showed that AA activated protein kinase B (AKT) signaling pathway in vivo and in vitro. Furthermore, we found that AA lost its protective effects in the heart with AKT inactivation. In conclusion, our results found that AA could attenuate DOX-induced myocardial oxidative stress and apoptosis via activation of the AKT signaling pathway.