Postconditioning with sevoflurane protects against focal cerebral ischemia and reperfusion injury via PI3K/Akt pathway
Postconditioning with sevoflurane protects against focal cerebral ischemia and reperfusion injury via PI3K/Akt pathway
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DOI：
10.1016/j.brainres.2010.08.009
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发表时间：
2010-10-21
期刊：
影响因子：
2.9
通讯作者：
Chen, Gao
中科院分区：
文献类型：
--
作者：
Wang, Jun-Kuan;Yu, Li-Na;Chen, Gao
新出现的证据表明，七氟醚的后处理提供了神经保护。本研究观察了不同浓度七氟醚对大脑中动脉闭塞(MCAO)大鼠的神经保护作用。此外，我们还验证了七氟醚后处理的神经保护作用与抑制细胞凋亡有关，并通过激活磷脂酰肌醇-3-激酶/Akt(PI3K/Akt)通路来实现。成年雄性SD大鼠大脑中动脉阻塞90min后，在再灌流开始时给予七氟醚治疗。24小时后评价脑梗塞体积、神经功能缺失评分和脑水肿程度。用Morris水迷宫检测大鼠的空间学习记忆能力。采用原位末端标记法、免疫组织化学法和免疫印迹法检测细胞凋亡及相关蛋白的表达。分析七氟醚加或不加Wortmannin后的神经保护作用和p-Akt的量。七氟醚1.0最低肺泡浓度(MAC)和1.5MAC后处理显著降低神经功能评分、脑梗塞体积和脑水肿，并显著改善空间学习和记忆。后处理还可减少细胞凋亡，上调Bcl2，下调P53和Bax的表达。Wortmannin消除神经保护作用，阻止p-Akt升高。我们的数据表明，七氟醚(1.0MAC和1.5MAC)的后处理不仅减少了脑梗塞体积，还改善了学习和记忆。我们的研究进一步表明，这种神经保护作用可能部分是由于激活了PI3K/Alct通路，抑制了神经元的凋亡。(C)2010爱思唯尔B.V.保留所有权利。
Emerging evidence has demonstrated that postconditioning with sevoflurane provided neuroprotection. In this study, we investigated the neuroprotective effect of different concentrations of sevoflurane in rats with middle cerebral artery occlusion (MCAO). Furthermore, we tested the hypothesis that the neuroprotective effect of postconditioning with sevoflurane is associated with inhibition of apoptosis and mediated by activation of the phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway. Adult male Sprague Dawley rats were subjected to MCAO for 90 min and then treated with sevoflurane at the beginning of reperfusion. The infarct volume, neurological deficit scores and brain edema were evaluated at 24 hours. Spatial learning and memory was examined by Morris water maze. Apoptosis and apoptosis-related proteins were studied by TUNEL, immunohistochemistry and western blot. The neuroprotective effect and the amount of p-Akt after sevoflurane administration with or without wortmannin were analyzed. Postconditioning with sevoflurane 1.0 minimum alveolar concentration (MAC) and 1.5 MAC significantly decreased neurological deficit scores, infarct volume and brain edema and markedly improved spatial learning and memory. Postconditioning also reduced apoptotic cells, upregulated Bcl-2 and downregulated P53 and Bax. Wortmannin abolished the neuroprotective effect and prevented the increasing of p-Akt. Our data suggest postconditioning with sevoflurane (1.0 MAC and 1.5 MAC) not only reduced infarct volume but also improved learning and memory. Our study further showed that this neuroprotective effect may be partly due to the activation of PI3K/Alct pathway and inhibiting neuronal apoptosis. (C) 2010 Elsevier B.V. All rights reserved.