右美托咪定对七氟醚所致幼鼠学习障碍和抑制突触蛋白表达的影响

Effects of dexmedetomidine on the learning disorder caused by sevoflurane and on the expression of synaptophysin in young rats

目的探讨右美托咪定对七氟醚所致幼鼠长期学习记忆障碍和对海马突触蛋白表达的影响。方法将7日龄SD幼鼠随机分为对照组,七氟醚组,右美托咪定组和七氟醚+右美托咪定组。麻醉后1 d和7 d采用western blot和RT-PCR测定海马内突触素、突触后致密物-95(PSD-95)和哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)蛋白和mRNA表达。5周后行Morris水迷宫测试。结果七氟醚麻醉后大鼠学习速度下降;七氟醚和右美托咪定均抑制幼鼠海马内突触素和PSD-95的蛋白表达和mRNA水平,右美托咪定显著减轻七氟醚的抑制作用。三种药物组合均显著抑制幼鼠海马内磷酸化mTOR(p-mTOR)蛋白和mTOR mRNA水平。结论右美托咪定可以减轻七氟醚所致幼鼠长期学习记忆障碍和对海马突触蛋白的抑制作用,这种保护作用并不是通过p-mTOR途径发挥作用的。

Objective To investigate the effects of dexmedetomidine on the dysfunction of memory and learning and the expression of synaptophysin as well as post synaptic density 95 （ PSD-95 ） in hippocampus caused by sevoflurane in young rats. Methods Ninety Sprague-Dawley rats （7-day age） were randomly divided to four groups, control group sevoflurane group, dexmedetomidine group and sevoflurane ＋ dexmedetomidine group （ Sev ＋ Dex group ）. The rats in sevoflurane group inhaled 2% sevoflurane for 4 hours, the rats in dexmedetomidine group received dexmedetomidine 25 μg/kg by intraperitoneal injection,the rats in Sev ＋ Dex group inhaled 2% sevoflurane after intraperitoneal injection for 4 hours. The levels of synaptophysin in hippoeampus, PSD 95 and p mammalian target of rapamycin （ p-mTOR ） protein and mRNA expression were detected by Westem Blot and RT-PCR at 1,7 days after anesthesia. The abilities of memory and learning were evaluated by using Morris Water Maze Test after 5 weeks. Results The speed of learning in sevoflurane group was decreased, as compared with that in control group, however, no obvious effect was found in dexmedetomidine group and Sev ＋ Dex group. Both sevoflurane and dexmedetomidine decreased the expression levels of synaptophysin and PSD 95 protein and reRAN, moreover, dexmedetomidine could obviously relieve the inhibition effect of sevoflurane on the expression of these proteins. The three drugs could all decrease the expression level of p-mTOR protein and mTOR mRAN. Conclusion Dexmedetomidine can relieve the inhibition effect of sevoflurane on the expression of synaptophysin and PSD 95 in hippocampus of young rats and can improve the dysfunction of memory and learning after sevflurane anesthesia, however, which is not performed through p-mTOR pathway.