Panax notoginseng saponins inhibit ischemia-induced apoptosis by activating PI3K/Akt pathway in cardiomyocytes
Panax notoginseng saponins inhibit ischemia-induced apoptosis by activating PI3K/Akt pathway in cardiomyocytes
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DOI：
10.1016/j.jep.2011.05.011
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发表时间：
2011-09-01
影响因子：
5.4
通讯作者：
Lin, Shuguang
中科院分区：
文献类型：
--
作者：
Chen, Shaoxian;Liu, Juli;Lin, Shuguang
目的：三七皂苷（PNS）在临床上用于治疗心血管疾病和脑卒中。有证据表明，PNS可保护心肌细胞免受缺血损伤，但其保护作用的分子机制尚不清楚。本研究旨在探讨PNS对体外大鼠心肌缺血损伤模型H9c2细胞凋亡的保护作用及其可能的分子机制。材料和方法：体外模型采用血清、葡萄糖和氧气剥夺（SGOD） H9c2细胞，体内模型采用左前降支冠状动脉结扎术SD大鼠。采用Annexin V/PI法和TUNEL法观察PNS的抗凋亡作用。JC-1法检测线粒体膜电位（Delta psi m）。western blot法检测Akt及磷酸化Akt （p-Akt）的表达。结果：PNS对H9c2细胞和缺血心肌组织均有抗凋亡作用。然而，这种作用在体外被特异性PI3k抑制剂LY294002阻断。PNS的抗凋亡作用是通过稳定H9c2细胞的δ psi m介导的。左室射血分数（EF）、左室缩短分数（FS）、舒张末期左室尺寸（LVDd）和收缩末期左室尺寸（LVDs）等指标表明PNS对大鼠心功能有改善作用。PNS在H9c2细胞和缺血心肌组织中均显著增加p-Akt， LY294002在H9c2细胞中也能阻断这一作用。结论：本研究结果提示PNS通过激活PI3K/Akt信号通路，对体外和体内模型心肌缺血诱导的心肌细胞凋亡具有保护作用。2011爱思唯尔爱尔兰有限公司版权所有。
Aim of this study: The panax notoginseng saponins (PNS) have been clinically used for the treatment of cardiovascular diseases and stroke in China. Evidences demonstrated that PNS could protect cardiomyocytes from injury induced by ischemia, but the underlying molecular mechanisms of this protective effect are still unclear. This study was aimed to investigate the protective effect and potential molecular mechanisms of PNS on apoptosis in H9c2 cells in vitro and rat myocardial ischemia injury model in vivo.Materials and methods: H9c2 cells subjected to serum, glucose and oxygen deprivation (SGOD) were used as in vitro models and SD rats subjected to left anterior descending (LAD) coronary artery ligation were used as in vivo models. The anti-apoptotic effect of PNS was evaluated by Annexin V/PI analysis or TUNEL assay. Mitochondrial membrane potential (Delta psi m) was detected by JC-1 analysis. The expression of Akt and phosphorylated Akt (p-Akt) were detected by western blot assay.Results: PNS exhibited anti-apoptotic effect both in H9c2 cells and in ischemic myocardial tissues. However, the effect was blocked in vitro by LY294002, a specific PI3k inhibitor. The anti-apoptotic effect of PNS was mediated by stabilizing Delta psi m in H9c2 cells. Furthermore the indices of the left ventricular ejection fractions (EF), left ventricular fractional shortening (FS), left ventricular dimensions at end diastole (LVDd) and left ventricular dimensions at end systole (LVDs) suggested that PNS improved rats cardiac function. PNS significantly increased p-Akt both in H9c2 cells and in ischemic myocardial tissues and this effect was also blocked by LY294002 in H9c2 cells.Conclusion: Results of this study suggested that PNS could protect myocardial cells from apoptosis induced by ischemia in both the in vitro and in vivo models through activating PI3K/Akt signaling pathway. (C) 2011 Elsevier Ireland Ltd. All rights reserved.