Vasculoprotective effect of insulin in the ischemic/reperfused canine heart: Role of Akt-stimulated NO production
Vasculoprotective effect of insulin in the ischemic/reperfused canine heart: Role of Akt-stimulated NO production
复制标题
胰岛素对缺血/再灌注犬心脏的血管保护作用：Akt 刺激 NO 产生的作用。
DOI：
10.1016/j.cardiores.2005.08.019
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发表时间：
2006-01-01
影响因子：
10.8
通讯作者：
Gao, F
中科院分区：
文献类型：
--
作者：
Ma, H;Zhang, HF;Gao, F
目的：本研究旨在探讨葡萄糖-胰岛素-钾（GIK）对缺血/再灌注所致冠状动脉内皮功能损伤的保护作用及其机制。再灌注前5 min静脉注射溶媒、GIK或GK，测定冠状动脉血管功能障碍和内皮细胞凋亡。在一项单独的研究中，培养的内皮细胞进行模拟缺血/再灌注，和参与胰岛素的抗凋亡作用的信号通路investigated.Results：在体内缺血/再灌注引起显着的冠状动脉血管内皮功能障碍，证明减少内皮依赖性血管舒张，减少一氧化氮（NO）的产生，和内皮细胞凋亡的caspase 3激活和TUNEL染色。GIK治疗显著改善内皮依赖性冠状动脉血管舒张（P < 0.01），增加总NO产生（P < 0.01），减少内皮细胞凋亡。在培养的内皮细胞中，胰岛素治疗也显着增加NO的产生，减少模拟缺血/再灌注诱导的细胞凋亡。此外，无论是Akt抑制剂或NO合成酶抑制剂预处理几乎取消了抗凋亡作用所施加的胰岛素，但不是由SNAP，NO donor.Conclusion：这些结果表明，在体内治疗GIK在再灌注减弱缺血/再灌注诱导的冠状动脉内皮功能障碍和内皮细胞凋亡的Akt依赖和NO介导的方式。胰岛素引起的冠状动脉血管保护作用可能有助于先前观察到的GIK的心脏保护作用。(c)2005年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objectives: The objectives of this study were to investigate the vasculoprotective effects of glucose- insulin-potassium (GIK) on ischemia/reperfusion-induced coronary endothelial functional injury and to elucidate the mechanism involved.Methods: Dogs were subjected to 50 min of coronary occlusion and 4 h of reperfusion. Vehicle, GIK, or GK were intravenously infused 5 min before reperfusion, and the coronary vascular dysfunction and endothelial apoptosis were determined. In a separate study, cultured endothelial cells were subjected to simulated ischemia/reperfusion, and the signaling pathway involved in insulin's anti-apoptotic effect was investigated.Results: In vivo ischemia/reperfusion caused significant coronary vascular endothelial dysfunction as evidenced by reduced endothelium-dependent vasorelaxation, decreased nitric oxide (NO) production, and endothelial cell apoptosis as determined by caspase 3 activation and TUNEL staining. Treatment with GIK, but not GK, markedly improved the endothelium-dependent coronary vasorelaxation (P < 0.01 versus vehicle), increased total NO production (P < 0.01), and attenuated endothelial apoptosis. In cultured endothelial cells, treatment with insulin also markedly increased NO production and reduced simulated ischemia/reperfusion-induced apoptosis. Moreover, pre-treatment with either Akt inhibitor or NO synthase inhibitor almost abolished the anti-apoptotic effect exerted by insulin but not by SNAP, an NO donor.Conclusion: These results demonstrate that in vivo treatment with GIK at reperfusion attenuates ischemia/reperfusion-induced coronary endothelial dysfunction and endothelial apoptosis in an Akt-dependent and NO-mediated fashion. The coronary vasculoprotective effect elicited by insulin may contribute to the previously observed cardiac protective effect of GIK. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.