Nutritional Preconditioning of Apigenin Alleviates Myocardial Ischemia/Reperfusion Injury via the Mitochondrial Pathway Mediated by Notch1/Hes1
Nutritional Preconditioning of Apigenin Alleviates Myocardial Ischemia/Reperfusion Injury via the Mitochondrial Pathway Mediated by Notch1/Hes1
复制标题
芹菜素营养预处理通过Notch1/Hes1介导的线粒体途径减轻心肌缺血/再灌注损伤
DOI：
10.1155/2019/7973098
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发表时间：
2019-01-01
影响因子：
--
通讯作者：
Liu, Jichun
中科院分区：
文献类型：
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作者：
Huang, Huang;Lai, Songqing;Liu, Jichun
芹菜素 (Api) 是一种在多种草药中含量丰富的天然黄酮，在临床研究中显示出强大的心脏保护作用，但其潜在机制尚不清楚。我们假设 Api 通过营养预处理 (NPC) 保护心肌免受模拟缺血/再灌注 (SI/R) 损伤。喂食含 Api 食物的老鼠显示出心脏功能的改善；乳酸脱氢酶（LDH）和肌酸磷酸激酶（CPK）活性；梗塞面积；细胞凋亡率；丙二醛（MDA）水平； caspase-3、超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH-Px) 和过氧化氢酶 (CAT) 活性；与 SI/R 损伤后饲喂标准食物的动物相比，铁含量降低了抗氧化能力 (FRAP)。此外，Api预处理显着提高了活力，降低了LDH活性和细胞内活性氧（ROS）的产生，减轻了线粒体膜电位（MMP）的损失，阻止了线粒体通透性转换孔（mPTP）的开放，并降低了caspase-3活性、细胞色素c（Cyt C）释放和细胞凋亡 原代心肌细胞中由 SI/R 诱导。从机制上讲，Api 上调 Hes1 表达，并被 Notch1 γ-分泌酶抑制剂 GSI 以及 mPTP 开启子白术苷 (Atr) 功能中和。综上所述，Api 通过 Notch1/Hes1 信号通路介导的线粒体通路保护心肌免受 SI/R 损伤。
Apigenin (Api), a natural flavone found in high amounts in several herbs, has shown potent cardioprotective effects in clinical studies, although the underlying mechanisms are not clear. We hypothesized that Api protects the myocardium from simulated ischemia/reperfusion (SI/R) injury via nutritional preconditioning (NPC). Rats fed with Api-containing food showed improvement in cardiac functions; lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) activities; infarct size; apoptosis rates; malondialdehyde (MDA) levels; caspase-3, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities; and ferric reducing antioxidant power (FRAP) compared to those fed standard chow following SI/R injury. In addition, Api pretreatment significantly improved the viability, decreased the LDH activity and intracellular reactive oxygen species (ROS) generation, alleviated the loss of mitochondrial membrane potential (MMP), prevented the opening of the mitochondrial permeability transition pore (mPTP), and decreased the caspase-3 activity, cytochrome c (Cyt C) release, and apoptosis induced by SI/R in primary cardiomyocytes. Mechanistically, Api upregulated Hes1 expression and was functionally neutralized by the Notch1 γ-secretase inhibitor GSI, as well as the mPTP opener atractyloside (Atr). Taken together, Api protected the myocardium against SI/R injury via the mitochondrial pathway mediated by the Notch1/Hes1 signaling pathway.