The role of phosphoinositide-3-kinase/Akt pathway in propofol-induced postconditioning against focal cerebral ischemia-reperfusion injury in rats
The role of phosphoinositide-3-kinase/Akt pathway in propofol-induced postconditioning against focal cerebral ischemia-reperfusion injury in rats
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DOI：
10.1016/j.brainres.2009.08.054
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发表时间：
2009-10-22
期刊：
影响因子：
2.9
通讯作者：
Wang, Ying
中科院分区：
文献类型：
--
作者：
Wang, Hai-yun;Wang, Guo-lin;Wang, Ying
本研究旨在探讨异丙酚是否对缺血性脑损伤具有后处理作用，以及PI3K/Akt通路在这一现象中的作用。老鼠接受了2 h的大脑中动脉阻塞(MCAO)其次是22 h(再灌注被随机分为9组(n = 15): sham-operated集团MCAO组,异丙酚10,20到35 mg.kg (1) . h(1)组(异丙酚10 20 35 mg.kg (1) . h(1)注入出现再灌注的30分钟),渥曼青霉素组(渥曼青霉素0.6毫克/公斤管理MCAO之前30分钟),和其他三组收到渥曼青霉素其次是10、20和35 mg.kg (1) . h(1)异丙酚。与单独MCAO组相比，10和20 mg.kg(-1).h（-1）剂量的异丙酚显著减少梗死体积，降低神经功能缺损评分，减轻神经元凋亡。瞬时MCAO后，异丙酚10和20 mg.kg(-1).h（-1）组缺血半暗区磷酸化Akt （P-Akt）升高。选择性PI3K抑制剂wortmannin部分消除了异丙酚诱导的缺血半暗带的神经保护作用和P-Akt表达升高。3S mg.kg(-1).h（-1）剂量的异丙酚对暂时性MCAO大鼠梗死面积、神经功能缺损评分、神经元凋亡及P-Akt水平无影响。综上所述，在再灌注开始时灌注10或20 mg.kg(-1).h（-1）剂量的异丙酚可对短暂性MCAO大鼠提供神经保护，异丙酚诱导的后适应作用部分是通过维持PI3K/Akt通路的活性来实现的。(c) 2009 Elsevier B.V.版权所有
The aim of this study was to investigate whether propofol could provide postconditioning to ischemic brain injury and the role of phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway in this phenomenon. Rats underwent 2 h of middle cerebral artery occlusion (MCAO) followed by 22 h of reperfusion were randomly divided into nine groups (n = 15 each): sham-operated group, MCAO group, propofol 10, 20 and 35 mg.kg(-1).h(-1) group (propofol 10, 20,35 mg.kg(-1).h(-1) infused at the onset of reperfusion for 30 min), wortmannin group (wortmannin 0.6 mg/kg administered 30 min before MCAO), and the other three groups received wortmannin followed by 10, 20 and 35 mg.kg(-1).h(-1) propofol respectively. Propofol at doses of 10 and 20 mg.kg(-1).h(-1) significantly reduced infarct volume, decreased neurological deficit scores and attenuated neuron apoptosis compared with MCAO group alone. Increased phosphorylated Akt (P-Akt) was observed in the ischemic penumbra of propofol 10 and 20 mg.kg(-1).h(-1) group after transient MCAO. The selective PI3K inhibitor, wortmannin partly eliminated the neuroprotective effect and the elevation of P-Akt expression in ischemic penumbra induced by propofol. Propofol at dose of 3S mg.kg(-1).h(-1) did not affect infarct volume, neurological deficit scores, neuronal apoptosis and the level of P-Akt in transient MCAO rats. Taken together, these results demonstrated that propofol at doses of 10 or 20 mg.kg(-1).h(-1) infused at the onset of reperfusion for 30 min could provide neuroprotection to transient MCAO rats, and the postconditioning effect induced by propofol partly through maintaining the activity of PI3K/Akt pathway. (c) 2009 Elsevier B.V. All rights reserved.