Wu Zhou, Zhu Shu-Zhen, Hu Ya-Fang, Gu Yong, Wang Sheng-Nan, Lin Zhen-Zhou, Xie Zuo-Shan, Pan Su-Yue
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Brain Res. 2016 Jul 15;1643:113-22. doi: 10.1016/j.brainres.2016.04.067. Epub 2016 Apr 28.
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 6h after MCAO onset, and then we assessed the effects of the combination of glibenclamide and hypothermia at 6, 8 or 10h after MCAO onset. At 24h 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 6h 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-α and IL-1β. 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.
为了评估格列本脲是否能延长诱导性低温对中风具有保护作用的治疗窗，我们将成年雄性Sprague-Dawley大鼠进行大脑中动脉闭塞（MCAO）。我们首先验证了在MCAO发作后0、2、4或6小时诱导的低温的保护作用，然后评估了在MCAO发作后6、8或10小时格列本脲与低温联合应用的效果。在MCAO后24小时，我们评估了脑水肿、梗死体积、改良神经功能缺损评分、伊文思蓝渗漏以及磺脲类受体1（SUR1）蛋白和促炎因子的表达。当MCAO后诱导低温时间过长时，未观察到保护作用。在MCAO发作后6小时，单独低温未能降低脑水肿和梗死体积，但格列本脲与低温联合应用可降低两者。联合应用还改善了神经功能结局，减轻了血脑屏障损伤，并降低了COX-2、TNF-α和IL-1β的水平。这些结果表明，格列本脲可能通过减轻血脑屏障损伤和降低促炎因子水平，增强并延长了延迟性低温对缺血性中风的治疗效果。
