Glibenclamide enhances the effects of delayed hypothermia after experimental stroke in rats
Glibenclamide enhances the effects of delayed hypothermia after experimental stroke in rats
复制标题
格列本脲增强大鼠实验性中风后延迟低温的作用
DOI：
10.1016/j.brainres.2016.04.067
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发表时间：
2016-07-15
期刊：
影响因子：
2.9
通讯作者：
Pan, Su-Yue
中科院分区：
文献类型：
--
作者：
Wu, Zhou;Zhu, Shu-Zhen;Pan, Su-Yue
为了评估格列本脲是否可以延长诱导低温可以预防中风的治疗窗，我们对成年雄性Sprague-Dawley大鼠进行大脑中动脉闭塞（MCAO）。我们首先验证了MCAO发生后0、2、4或6小时诱导的低温的保护作用，然后评估了MCAO发生后6、8或10小时格列本脲和低温联合使用的效果。在MCAO后24 h，我们评估了脑水肿、梗死体积、改良的神经系统严重程度评分、伊文思蓝渗漏以及磺酰脲受体1（SUR 1）蛋白和促炎因子的表达。当MCAO后诱导低温时间过长时，没有观察到保护作用。在MCAO发病后6小时，单独低温不能减少脑水肿和梗死体积，但格列本脲和低温的组合减少两者。该组合还改善了神经学结果，改善了血脑屏障损伤，并降低了考克斯-2、TNF-α和IL-1 β的水平。这些结果表明，格列本脲可能通过改善血脑屏障损伤和降低促炎因子水平来增强和延长延迟低温治疗缺血性中风的治疗效果。(c)© 2016 Elsevier B. V.版权所有。
In order to evaluate whether glibenclamide can extend the therapeutic window during which induced hypothermia can protect against stroke, we subjected adult male Sprague-Dawley rats to middle cerebral artery occlusion (MCAO). We first verified the protective effects of hypothermia induced at 0, 2, 4 or 6 h after MCAO onset, and then we assessed the effects of the combination of glibenclamide and hypothermia at 6, 8 or 10 h after MCAO onset. At 24 h after MCAO, we assessed brain edema, infarct volume, modified neurological severity score, Evans Blue leakage and expression of Sulfonylurea receptor 1 (SUR1) protein and pro-inflammatory factors. No protective effects were observed when hypothermia was induced too long after MCAO. At 6 h after MCAO onset, hypothermia alone failed to decrease cerebral edema and infarct volume, but the combination of glibenclamide and hypothermia decreased both. The combination also improved neurological outcome, ameliorated blood-brain barrier damage and decreased levels of COX-2, TNF-alpha and IL-1 beta. These results suggest that glibenclamide enhances and extends the therapeutic effects of delayed hypothermia against ischemia stroke, potentially by ameliorating blood-brain barrier damage and declining levels of pro-inflammatory factors. (c) 2016 Elsevier B.V. All rights reserved.