Huang Kai-Yu, Yu Yong-Wei, Liu Shuai, Zhou Ying-Ying, Wang Jin-Sheng, Peng Yang-Pei, Ji Kang-Ting, Xue Yang-Jing
Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China.
Department of Endocrinology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China.
Front Pharmacol. 2021 Jul 19;12:642925. doi: 10.3389/fphar.2021.642925. eCollection 2021.
Myocardial ischemia-reperfusion (I/R) injury, characterized by myocardial cell death (e.g., apoptosis) and generation of reactive oxygen species (ROS) such as superoxide (O ) and hydrogen peroxide (HO), is a serious threat to human health and property. Saponin astragaloside IV (ASIV), extracted from Chinese herbal medicine astragalus, is effective in resolving multiple pathological issues including myocardial I/R injury. Recent studies have shown that autophagy is regulated by ROS and plays an important role in myocardial I/R injury. However, regulation of autophagy by ASIV during myocardial I/R injury and the role of specific ROS involved in the process have been rarely reported. In the present study, we found that SOD2 was downregulated and O was upregulated in HO-induced H9C2 cardiac myocyte injury and myocardial I/R injury , while such alterations were reversed by ASIV. ASIV possessed the ability to alleviate myocardial I/R injury via attenuating I/R-caused autophagosome accumulation. Upregulate of O by 2-methoxyestradiol (2-ME) reversed the effect of ASIV-mediated autophagy regulation, which suggested that O was vital in this process. In conclusion, our results contribute to understanding the mechanism of ASIV-induced cardioprotective effect.
心肌缺血再灌注(I/R)损伤以心肌细胞死亡(如凋亡)以及超氧阴离子(O )和过氧化氢(H₂O₂)等活性氧(ROS)的产生为特征,对人类健康和生命构成严重威胁。从中药黄芪中提取的皂苷黄芪甲苷(ASIV),对解决包括心肌I/R损伤在内的多种病理问题有效。最近的研究表明,自噬受ROS调节,并在心肌I/R损伤中起重要作用。然而,ASIV在心肌I/R损伤期间对自噬的调节以及该过程中特定ROS的作用鲜有报道。在本研究中,我们发现超氧化物歧化酶2(SOD2)在过氧化氢诱导的H9C2心肌细胞损伤和心肌I/R损伤中表达下调,而超氧阴离子上调,而ASIV可逆转这些改变。ASIV具有通过减轻I/R引起的自噬体积累来减轻心肌I/R损伤的能力。2-甲氧基雌二醇(2-ME)上调超氧阴离子可逆转ASIV介导的自噬调节作用,这表明超氧阴离子在该过程中至关重要。总之,我们的结果有助于理解ASIV诱导心脏保护作用的机制。