Jia Zhen, Geng Lina, Xie Guanglun, Chu Qinjun, Zhang Wei
Department of Anesthesiology, First Affiliated Hospital of Zhengzhou University China ; Department of Anesthesiology, Henan Provincial Corps Hospital China.
Department of Information, Henan Provincial Corps Hospital China.
Int J Clin Exp Med. 2015 Sep 15;8(9):15490-7. eCollection 2015.
To investigate the mechanism and effect of sevoflurane on learning and memory function in transgenic mice model of Alzheimer's disease (AD).
A total of 45 Tg2576 mice were used and randomly assigned to control, sham, and sevoflurane group. Spatial learning and memory ability were measured before and after sevoflurane exposure using morris water maze (MWM) and Y-maze behavioral tests. Moreover, TUNEL assay was carried out to determine the cell death in hippocampal cornuammonis (CA) 1, CA3, and dentate gyrus (DG) region. Apoptosis-related protein (caspase-3 and Bcl-xL) expression in the hippocampus was analyzed by Western blotting.
The MWM results showed that there were no significant differences in the swimming speed after sevoflurane exposure among the three groups. However, the escape latency, time spent in original quadrant, and the number of correct trials (Y-maze) were significantly lower after sevoflurane anesthesia exposure in the sevoflurane group than the sham group and control group (P < 0.05). Besides, the apoptotic cell numbers of the CA1 and CA3 region in the sevoflurane group were significantly higher than those in the sham group and control group (P < 0.05). Western blotting results showed that the protein expression levels of Bcl-xL were significantly higher, but the caspase-3 levels were significantly lower in the sevoflurane group than those in the control group and sham group (both P < 0.05).
Our results indicate that sevoflurane might impair acquisition learning and memory function in AD by induction of hippocampal neuron apoptosis.
探讨七氟醚对阿尔茨海默病（AD）转基因小鼠模型学习记忆功能的作用机制及影响。
共使用45只Tg2576小鼠，随机分为对照组、假手术组和七氟醚组。在七氟醚暴露前后，采用莫里斯水迷宫（MWM）和Y迷宫行为测试来测量空间学习和记忆能力。此外，进行TUNEL检测以确定海马角回（CA）1、CA3和齿状回（DG）区域的细胞死亡情况。通过蛋白质免疫印迹法分析海马中凋亡相关蛋白（caspase-3和Bcl-xL）的表达。
MWM结果显示，七氟醚暴露后三组小鼠的游泳速度无显著差异。然而，七氟醚组七氟醚麻醉暴露后的逃避潜伏期、在原象限停留的时间以及正确试验次数（Y迷宫）均显著低于假手术组和对照组（P<0.05）。此外，七氟醚组CA1和CA3区域的凋亡细胞数显著高于假手术组和对照组（P<0.05）。蛋白质免疫印迹结果显示，七氟醚组Bcl-xL的蛋白表达水平显著高于对照组和假手术组，但caspase-3水平显著低于对照组和假手术组（均P<0.05）。
我们的结果表明，七氟醚可能通过诱导海马神经元凋亡损害AD小鼠的学习和记忆功能。
