Ischemic preconditioning activates prosurvival kinases and reduces myocardial apoptosis
Ischemic preconditioning activates prosurvival kinases and reduces myocardial apoptosis
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DOI：
10.1016/j.jcma.2015.04.006
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发表时间：
2015-08-01
影响因子：
3
通讯作者：
Huang, Cheng-Hsiung
中科院分区：
文献类型：
--
作者：
Lai, Chang-Chi;Tang, Chia-Yu;Huang, Cheng-Hsiung
背景：缺血预处理对心肌缺血再灌注损伤具有保护作用。其潜在机制已被广泛研究，但尚未完全阐明。在这项研究中，我们研究了细胞凋亡在缺血预处理保护中的作用和参与的信号通路。方法：在麻醉的雄性Sprague道利大鼠中，通过阻断左冠状动脉前降支40分钟和再灌注3小时来诱导心肌缺血和再灌注。结果：缺血预处理组心肌梗死面积（以危险面积百分比表示）明显减少（缺血组和再灌注组分别为16.8 ± 2.0%和27.9 ± 2.7%，p < 0.001）。此外，缺血预处理显着减少细胞凋亡，这一点可以通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记阳性细胞核、DNA梯状排列和caspase-3激活的减少来证明。免疫印迹分析显示，缺血预处理显著降低心肌肿瘤坏死因子-a水平。心肌Bcl-2表达增加，Bax表达减少。促生存激酶的磷酸化，包括Akt和细胞外信号调节激酶1和2，显着增加。血流动力学，危险区，死亡率并没有显着groups.Conclusion：缺血预处理减少心肌缺血和再灌注诱导的细胞凋亡。其机制可能与抑制肿瘤坏死因子-α的产生、调节Bcl-2和Box的表达以及激活促生存激酶从而抑制外源性和内源性凋亡途径有关。版权所有（C）2015 Elsevier Taiwan LLC及中华医学会。All rights reserved.
Background: Ischemic preconditioning has been reported to protect the myocardium against ischemia and reperfusion injury. The underlying mechanisms have been extensively investigated but are not fully elucidated. In this study, we investigated the role of apoptosis in ischemic preconditioning protection and the signal pathways involved.Methods: Myocardial ischemia and reperfusion were induced in anesthetized male Sprague Dawley rats by a 40-minute occlusion and a 3-hour reperfusion of the left anterior descending coronary artery. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and two 10-minute reperfusions.Results: The myocardial infarct size, expressed as the percentage of area at risk, was significantly decreased in the ischemic preconditioning group (16.8 +/- 2.0% and 27.9 +/- 2.7% in the ischemia and reperfusion groups, respectively, p < 0.001). Additionally, ischemic preconditioning significantly reduced apoptosis, as evidenced by the decrease in the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei, DNA laddering, and caspase-3 activation. Western blot analysis revealed that ischemic preconditioning significantly reduced myocardial tumor necrosis factor-a levels. Bcl-2 was increased, whereas Bax was decreased in the myocardium. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2, was significantly increased. Hemodynamics, area at risk, and mortality did not differ significantly among the groups.Conclusion: Ischemic preconditioning reduces apoptosis induced by myocardial ischemia and reperfusion. The underlying mechanisms might be related to inhibition of both the extrinsic and the intrinsic apoptotic pathway via inhibition of production of tumor necrosis factor-a, modulation of expression of Bcl-2 and Box, and activation of the prosurvival kinases. Copyright (C) 2015 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved.