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目的探讨抗癫痫药丙戊酸钠(VPA)、奥卡西平(OXC)、左乙拉西坦(LEV)对大鼠认知、海马谷氨酸受体2(GluR2)和突触体素(Syn)表达的影响。方法随机将60只Wistar大鼠分为正常对照组(CON组)、VPA组、LEV组、OXC组、LEV+VPA组、LEV+OXC组,每组10只,灌胃给药,90 d后行Moriss水迷宫和穿梭箱实验测试,比较各组大鼠的空间和条件性学习记忆能力,采用免疫组化技术检测海马GluR2和Syn的表达。结果与对照组比较,VPA组水迷宫测试逃避潜伏期、正确率、运行时间及穿梭箱实验主动回避次数、主动回避潜伏期、被动回避潜伏期差异均有统计学意义(P均<0.05),免疫组化检测显示,VPA组GluR2和Syn的表达及LEV+VPA组的GluR2表达显著下降(P均<0.05)。结论 LEV、OXC、LEV+OXC、LEV+VPA不影响认知功能,VPA影响认知功能可能与其使GluR2和Syn的表达下降有关。
Objective To investigate the effects of antiepileptic drugs VPA, OXC and LEV on the cognition, glutamate receptor 2 (GluR2) and synaptophysin Syn) expression. Methods 60 Wistar rats were randomly divided into normal control group (CON group), VPA group, LEV group, OXC group, LEV + VPA group and LEV + OXC group. The Moriss water maze and shuttle box were used to test the spatial and conditional learning and memory abilities of rats in each group. The expressions of GluR2 and Syn in hippocampus were detected by immunohistochemistry. Results Compared with the control group, the evasion latency, correct rate, running time and the number of active avoidance, active avoidance and passive avoidance latency of VPA group were significantly different (P <0.05) The results showed that the expression of GluR2 and Syn in VPA group and GluR2 expression in LEV + VPA group were significantly decreased (all P <0.05). Conclusions LEV, OXC, LEV + OXC and LEV + VPA do not affect cognitive function. The influence of VPA on cognitive function may be related to the decrease of GluR2 and Syn expression.