Qiliqiangxin Attenuates Oxidative Stress-Induced Mitochondrion-Dependent Apoptosis in Cardiomyocytes <i>via</i> PI3K/AKT/GSK3β Signaling Pathway

作者：Qifei Zhao, Hongrong Li, Liping Chang, Cong Wei, Yujie Yin, Hongying Bei, Zhixin Wang, Junqing Liang, Yiling Wu · 发表于：Biological and Pharmaceutical Bulletin · 年份：2019 · DOI：10.1248/bpb.b19-00050 · 被引用次数：53 · 研究领域：Mitochondrial Function and Pathology、Cell death mechanisms and regulation、Cardiac Ischemia and Reperfusion

Qiliqiangxin capsule (QLQX) is a well-known traditional Chinese medicine that exhibits cardioprotective effects in heart failure patients. However, it remains unclear whether and by which mechanism QLQX attenuates oxidative stress-induced mitochondria-dependent myocardial apoptosis. In vivo, Sprague Dawley (SD) rats received left anterior descending coronary artery ligation for 4 weeks to establish a model of heart failure after acute myocardial infarction, and then were treated with QLQX for another 4 weeks. We evaluated cardiac function, oxidative stress injury, as well as the expressions of mitochondria-dependent apoptosis and its signaling factors. The results indicated that QLQX protected cardiac function and attenuated oxidative stress-induced myocardial apoptosis. Meanwhile, QLQX elevated the Bcl-2 expression, declined the expressions of Bax, cytochrome c, apoptotic protease activating factor-1 (Apaf-1), cleaved-caspase 9 and cleaved-caspase 3, and up-regulated the ratios of phospho-AKT/AKT and phospho-glycogen synthase kinase-3β (GSK3β)/GSK3β. In vitro, H9c2 cardiomyocytes were pretreated with QLQX, then exposed to H2O2 for 24 h. QLQX promoted the proliferation of H9c2 cardiomyocytes induced by H2O2 and reversed oxidative stress damage. Moreover, QLQX inhibited the apoptosis rate and the pro-apoptosis protein expressions, but improved the Bcl-2 expression as well as the ratios of phospho-AKT/AKT and phospho-GSK3β/GSK3β. Meanwhile, it further ameliorated mitochondrion-...