奥拉西坦对七氟烷诱发小鼠认知功能障碍的影响:PI3K/Akt信号通路在其中的作用

Effect of oxiracetam on sevoflurane-induced cognitive dysfunction in mice:role of PI3K/Akt signaling pathway

目的评价奥拉西坦对七氟烷诱发小鼠认知功能障碍的影响及磷脂酰肌醇3-激酶/丝苏氨酸蛋白激酶(PI3K/Akt)信号通路在其中的作用。方法成年昆明小鼠80只,雌雄各半,体重35~55 g,采用随机数字表法分为4组(n=20):对照组(C组)、七氟烷组(S组)、奥拉西坦+七氟烷组(OS组)和LY294002+奥拉西坦+七氟烷组(LOS组)。S组吸入2%七氟烷6 h;于七氟烷麻醉前2 h时,OS组尾静脉注射奥拉西坦105 mg/kg,LOS组尾静脉注射奥拉西坦105 mg/kg和LY2940020.3 mg/kg,S组注射等容量生理盐水。麻醉结束后6 h时,采用TUNEL法确定海马神经细胞凋亡率,采用Western blot法测定PI3K、磷酸化PI3K(p-PI3K)、Akt和磷酸化Akt(p-Akt)的表达。麻醉结束后14 d时,采用Y迷宫测定认知功能。结果与C组比较,S组海马神经细胞凋亡率升高,Y迷宫中10次全对所需总次数和错误次数增多,海马PI3K、Akt、p-PI3K和p-Akt表达下调(P<0.05);与S组比较,OS组海马神经细胞凋亡率降低,Y迷宫中10次全对所需总次数和错误次数减少,海马PI3K、Akt、p-PI3K和p-Akt表达上调(P<0.05),LOS组上述指标差异无统计学意义(P>0.05)。与OS组比较,LOS组海马神经细胞凋亡率升高,Y迷宫中10次全对所需总次数和错误次数增多,海马PI3K、Akt、p-PI3K和p-Akt表达下调(P<0.05)。结论奥拉西坦可减轻七氟烷诱发的小鼠认知功能障碍,机制可能与激活PI3K/Akt信号通路,抑制神经细胞凋亡有关。

Objective To evaluate the effect of oxiracetam on sevoflurane-induced cognitive dysfunction in mice and the role of phosphatidylinositol 3-kinase/serine/threonine protein kinase(PI3K/Akt)signaling pathway.Methods Eighty adult Kunming mice,half male and half female,weighing 35-55 g,were divided into 4 groups(n=20 each)using a random number table method:control group(group C),sevoflurane group(group S),oxiracetam plus sevoflurane group(group OS),and LY294002 plus oxiracetam plus sevoflurane group(group LOS).Group S inhaled 2%sevoflurane for 6 h.A 2 h before sevoflurane anesthesia,oxiracetam 105 mg/kg was injected via the tail vein in group OS,oxiracetam 105 mg/kg and LY2940020.3 mg/kg were injected via the tail vein in group LOS,and the equal volume of normal saline was injected in group S.The apoptosis rate of hippocampal neurons was detected using TUNEL.The expression of PI3K,phosphorylated PI3K(p-PI3K),Akt and phosphorylated Akt(p-Akt)was determined by Western blot.Cognitive function was assessed using Y-maze at 14 days after the end of anesthesia.Results Compared with group C,the apoptosis rate of hippocampal neurons was significantly increased,the total number of times and the number of errors required for 10 times of correct responses in Y-maze test were increased,and the expression of PI3K,Akt p-PI3K and p-Akt in hippocampal tissues was down-regulated in group S(P<0.05).Compared with group S,the apoptosis rate of hippocampal neurons was significantly decreased,the total number of times and the number of errors required for 10 times of correct responses in Y-maze test were decreased,the expression of PI3K,Akt,p-PI3K and p-Akt in hippocampal tissues was up-regulated in group OS(P<0.05),and no significant changes were found in the parameters mentioned above in group LOS(P>0.05).Compared with group OS,the apoptosis rate of hippocampal neurons was significantly increased,the total number of times and the number of errors required for 10 times of correct responses in Y-maze test were increased,and the expression of PI3K,Akt,p-PI3K and p-Akt in hippocampal tissues was down-regulated in group LOS(P<0.05).Conclusion Oxiracetam can alleviate sevoflurane-induced cognitive dysfunction in mice,and the mechanism may be related to activating PI3K/Akt signaling pathway and inhibiting apoptosis in neurons.