Acute administration of ethanol reduces apoptosis following ischemic stroke in rats
Acute administration of ethanol reduces apoptosis following ischemic stroke in rats
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DOI：
10.1016/j.neures.2013.02.011
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发表时间：
2013-05-01
影响因子：
2.9
通讯作者：
Ding, Yuchuan
中科院分区：
文献类型：
--
作者：
Fu, Paul;Peng, Changya;Ding, Yuchuan
在最近的研究中，急性乙醇给药似乎在缺血性中风中起神经保护作用。我们试图通过确定乙醇来源的神经保护是否与细胞凋亡减少有关来证实这些发现。在大脑中动脉（MCA）闭塞2小时后，以0.5和1.5 g/kg剂量的乙醇腹腔注射Sprague-Dawley大鼠，再灌注。采用酶联免疫吸附法（ELISA）定量各组凋亡细胞死亡情况，Western blot检测凋亡蛋白表达。大鼠缺血后细胞死亡明显增加，随后1.5 g/kg乙醇显著降低细胞死亡。我们发现，在再灌注后3 h， 1.5 g/kg剂量可促进促生存因子的表达，降低凋亡蛋白的表达。Caspase-3和凋亡诱导因子（AIF）在24小时内保持这种作用，但Bcl-2、Bcl-xL和Bcl-2相关X （Bax）则没有这种作用。0.5 g/kg乙醇对蛋白质表达的调节效果不如1.5 g/kg乙醇。我们的研究表明，中风后给予1.5 g/kg剂量的乙醇（使大鼠血液中的酒精含量相当于法定驾驶限制）会产生不同的蛋白质谱，抗凋亡蛋白的表达增加，促凋亡因子的表达减少。这导致神经元凋亡显著减少，在缺血再灌注损伤中具有神经保护作用。由爱思唯尔爱尔兰有限公司和日本神经科学学会出版
In recent studies, acute ethanol administration appears to play a neuroprotective role during ischemic stroke. We sought to confirm these findings by identifying if ethanol-derived neuroprotection is associated with a reduction in apoptosis.Ethanol at 0.5 and 1.5 g/kg doses was given by intraperitoneal injections to Sprague-Dawley rats after 2 h of middle cerebral artery (MCA) occlusion, followed by reperfusion. We quantified apoptotic cell death in each of the treatment groups with ELISA, and measured pro- and anti-apoptotic protein expression with Western blot analysis.Cell death was significantly increased in rats after ischemia and was subsequently significantly reduced by the administration of 1.5 g/kg of ethanol. We found that the 1.5 g/kg dose promoted the expression of pro-survival factors and decreased the expression of apoptotic proteins at 3 h after reperfusion. This effect was maintained at 24 h for Caspase-3 and apoptosis-inducing factor (AIF), although not for Bcl-2, Bcl-xL, and Bcl-2-associated X (Bax). Administration of 0.5 g/kg of ethanol was not as effective in regulating protein expression as the 1.5 g/kg dose.Our study suggests that administration of ethanol at a dose of 1.5 g/kg after stroke - which provides rat blood alcohol levels equivalent to the legal driving limit - produces a differential protein profile, with increased expression of anti-apoptotic proteins and decrease in pro-apoptotic factors. This results in a significant reduction of neuronal apoptosis and is neuroprotective in ischemia-reperfusion injury. Published by Elsevier Ireland Ltd and the Japan Neuroscience Society