Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
Department of Thoracic Cardiovascular Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, China.
Oxid Med Cell Longev. 2020 May 15;2020:5347204. doi: 10.1155/2020/5347204. eCollection 2020.
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.
阿魏酸（AA）可减轻多种心血管疾病引起的心肌损伤，但AA 是否能减轻 DOX 相关的心肌损伤尚不清楚。我们的研究数据发现，AA 处理的小鼠在注射 DOX 后表现出心脏损伤减轻和心功能改善。AA 还抑制心肌氧化损伤和细胞凋亡，但不影响 DOX 处理的小鼠的心脏炎症。AA 还为 DOX 刺激的心肌细胞提供保护，提高细胞活力，并在体外抑制细胞内活性氧（ROS）。对信号通路的检测表明，AA 在体内和体外激活蛋白激酶 B（AKT）信号通路。此外，我们发现 AKT 失活后 AA 在心脏中的保护作用丧失。综上所述，我们的结果发现 AA 通过激活 AKT 信号通路减轻 DOX 诱导的心肌氧化应激和细胞凋亡。
