Astragaloside IV protects cardiomyocytes from anoxia/reoxygenation injury by upregulating the expression of Hes1 protein.
Astragaloside IV protects cardiomyocytes from anoxia/reoxygenation injury by upregulating the expression of Hes1 protein.
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DOI：
10.1139/cjpp-2015-0457
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发表时间：
2016-05
影响因子：
2.1
通讯作者：
Huang Huang-Huang;S. Lai;Qing Wan;W. Qi;Jichun Liu
中科院分区：
文献类型：
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作者：
Huang Huang-Huang;S. Lai;Qing Wan;W. Qi;Jichun Liu
黄芪甲苷（Astragaloside IV，ASI）是黄芪的主要活性成分，是一种传统中药.许多临床研究发现ASI对心血管疾病中的心肌细胞有保护作用，但其机制尚不清楚。本研究旨在探讨黄芪注射液对心肌细胞缺氧/复氧（A/R）损伤保护作用的分子机制。根据前人的研究，我们推测ASI对A/R损伤的心肌保护作用可能与Notch 1/Hes 1信号通路有关。在这项研究中，新生大鼠原代心肌细胞预处理与ASI之前，A/R损伤。结果表明，黄芪甲苷能有效地提高细胞活力，降低MDA含量，降低CPK和LDH活性，提高GSH-Px和SOD活性，减少活性氧（ROS）的产生和线粒体膜电位（Δ Km）的损失。黄芪注射液可抑制心肌细胞线粒体通透性转换孔（mPTP）开放和caspase-3活化，从而减少心肌细胞凋亡。此外，ASI上调Hes 1蛋白表达。而Notch 1抑制剂DAPT预处理可有效抑制ASI对A/R损伤的心肌保护作用，但降低MDA、SOD、GSH-Px和ROS的生成。综上所述，我们证明了ASI可以通过Notch 1/Hes 1信号通路保护A/R损伤。
Astragaloside IV (ASI), a traditional Chinese medicine, is a main active ingredient of Astragalus membranaceus. Many clinical studies have found that ASI protects cardiomyocytes in cardiovascular diseases, but the underlying mechanisms remain obscure. The aim of this study was to investigate the molecular mechanisms responsible for the protective effects of ASI in cardiomyocytes from anoxia/reoxygenation (A/R) injury. According to the previous studies, we hypothesized that the cardioprotective effects of ASI against A/R injury might be associated with Notch1/Hes1 signaling pathway. In this study, neonatal rat primary cardiomyocytes were preconditioned with ASI prior to A/R injury. Our results showed that ASI effectively increased the cell viability, decreased the content of MDA, decreased the activities of CPK and LDH, increased the activities of GSH-Px and SOD, and reduced the reactive oxygen species (ROS) generation and the loss of mitochondrial membrane potential (Δψm). ASI inhibited the mitochondrial permeability transition pore (mPTP) opening and activation of caspase-3, and finally decreased the cell apoptosis in cardiomyocytes. Furthermore, ASI upregulated Hes1 protein expression. However, pretreatment with DAPT, a Notch1 inhibitor, effectively attenuated the cardioprotective effects of ASI against A/R injury, except MDA, SOD, GSH-Px, and the ROS generation. Taken together, we demonstrated that ASI could protect against A/R injury via the Notch1/Hes1 signaling pathway.