BackgroundWe aimed to study the role of amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) glutamate receptor 2 (GluR2) subunit trafficking, and activity changes in short-term neuroprotection provided by propofol post-conditioning. We also aimed to determine the role of phosphoinositide-3-kinase (PI3K) in the regulation of these processes.MethodsRats underwent 1 h of focal cerebral ischemia followed by 23 h of reperfusion were randomly divided into 6 groups (n = 36 per group): sham- operation (S), ischemia–reperfusion (IR), propofol (P group, propofol 20 mg/kg/h at the onset of reperfusion for 2 h after 60 min of occlusion), and LY294002 (PI3K non-selective antagonist) + sham (L + S, LY294002 of 1.5 mg/kg was infused 30 min before sham operation), LY294002+ ischemia–reperfusion (L + IR, LY294002 of 1.5 mg/kg was infused 30 min before middle cerebral artery occlusion), LY294002 + IR + propofol (L + P, LY294002 of 1.5 mg/kg was infused 30 min before middle cerebral artery occlusion and propofol 20 mg/kg/h at the onset of reperfusion for 2 h after 60 min of occlusion).ResultsCompared with group IR, rats in group P had significant lower neurologic defect scores and infarct volume. Additionally, consistent with enhanced expression of PI3K-AMPAR GluR2 subunit complex substances in ipsilateral hippocampus, GluR2 subunits showed increased levels in both the plasma and postsynaptic membranes of neurons, while pGluR2 expression was reduced in group P. Furthermore, LY294002, the PI3K non-selective antagonist, blocked those effects.ConclusionThese observations demonstrated that propofol post-conditioning revealed acute neuroprotective role against transient MCAO in rats. The short-term neuroprotective effect was contributed by enhanced GluR2 subunits trafficking to membrane and postsynaptic membranes of neurons, as well as down-regulated the expression of pGluR2 in damaged hippocampus. Finally, the above-mentioned protective mechanism might be contributed by increased combination of PI3K to AMPAR GluR2 subunit, thus maintained the expression and activation of AMPAR GluR2 in the ipsilateral hippocampus.

中文翻译：

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PI3K介导的AMPA受体变化在丙泊酚后处理脑保护中的作用

背景我们旨在研究氨基-3-羟基-5-甲基异恶唑-4-丙酸受体 (AMPAR) 谷氨酸受体 2 (GluR2) 亚基运输的作用，以及丙泊酚后处理提供的短期神经保护活性变化。我们还旨在确定磷酸肌醇-3-激酶 (PI3K) 在这些过程的调节中的作用。 方法将大鼠进行 1 小时局灶性脑缺血，然后再灌注 23 小时，随机分为 6 组（每组 n = 36） ：假手术 (S)、缺血再灌注 (IR)、丙泊酚（P 组，在闭塞 60 分钟后再灌注开始时丙泊酚 20 毫克/公斤/小时）和 LY294002（PI3K 非选择性拮抗剂） ) + 假手术（L + S，假手术前 30 分钟输注 1.5 mg/kg 的 LY294002），LY294002+ 缺血-再灌注（L + IR，LY294002 为 1。大脑中动脉闭塞前 30 分钟输注 5 mg/kg），LY294002 + IR + 丙泊酚（L + P，LY294002 1.5 mg/kg 在大脑中动脉闭塞前 30 分钟输注，丙泊酚 20 mg/kg/h 在大脑中动脉闭塞前输注）闭塞60 min后开始再灌注2 h。结果与IR组相比，P组大鼠神经功能缺损评分和梗死体积显着降低。此外，与同侧海马中 PI3K-AMPAR GluR2 亚基复合物质的表达增强一致，GluR2 亚基在神经元的质膜和突触后膜中的水平升高，而 pGluR2 的表达在 P 组中降低。此外，LY294002，PI3K 非选择性拮抗剂，阻断了这些作用。结论这些观察结果表明，丙泊酚后处理显示出对大鼠短暂性 MCAO 的急性神经保护作用。短期神经保护作用是由增强的 GluR2 亚基运输到神经元的膜和突触后膜以及下调受损海马中 pGluR2 的表达所贡献的。最后，上述保护机制可能是由于PI3K与AMPAR GluR2亚基的结合增加，从而维持了同侧海马中AMPAR GluR2的表达和激活。