托吡酯对癫大鼠认知功能及海马组织中NCAM的mRNA表达影响

The effects of topiramate on cognitive function and NCAM expression in hippocampus of epilepsy rats

目的研究托吡酯(TPM)对癫大鼠认知功能的影响以及使用TPM后大鼠海马组织中神经细胞粘附分子(NCAM)的mRNA表达变化。方法将大鼠随机分成生理盐水(NS)组、癫(EP)组、癫+托吡酯治疗1周(TPM1周)组和癫+托吡酯治疗4周(TPM4周)组,建立匹罗卡品诱导癫大鼠模型和TPM干预模型,观察大鼠的行为学改变,通过Morris水迷宫实验测试大鼠的学习记忆能力,并通过Real-TimePCR检测大鼠海马组织中NCAM的mRNA表达水平。结果EP组大鼠的逃避潜伏期大于NS组,原平台象限游泳时间百分比小于NS组,海马NCAM的mRNA表达水平高于NS组(P<0.01);TPM1周组和TPM4周组大鼠的逃避潜伏期大于EP组,原平台象限游泳时间百分比小于EP组,海马NCAM的mRNA表达水平低于EP组(P<0.01);TPM4周组大鼠的逃避潜伏期大于TPM1周组,原平台象限游泳时间百分比小于TPM1周组,海马NCAM的mRNA表达水平低于TPM1周组(P<0.05)。结论大鼠产生癫持续状态后认知功能明显下降,海马NCAM的mRNA表达上调;使用大剂量TPM短期治疗后其认知功能进一步下降,海马NCAM的mRNA表达受抑,且下降与受抑程度与TPM的持续使用时间有关。

Objective To explore the effects of topiramate （TPM） on cognitive function and nerve cell adhesion molecule （NCAM） expression in hippocampus of epilepsy rats. Methods Rats were randomly divided into NS, EP, TPM lw and TPM 4w groups, to found the models of epilepsy rats induced by pilocarpine and treated by TPM for one or four weeks. The rats were observed in behavior. Learning and memory abilities of the rats were determined by Morries water maze test, and NCAM mRNA expression in the rats＇ hippocampus were determined by Real-Time PCR. Results In group EP, the mean escape latency was higher, the percentage of swimming time was lower and the mRNA expression of NCAM was higher than in group NS （P〈0.01）; In groups TPM lw and TPM 4w, the mean escape latency was higher, the percentage of swimming time was lower and the mRNA expression of NCAM was lower than in group EP （P〈0. 01 ） ; In group TPM 4w, the mean escape latency was increased, the percentage of swimming time was decreased and the mRNA expression of NCAM was down-regulated, when compared with group TPM 1w （P〈0. 05）. Conclusions Status epilepticus could reduce rats＇ cognitive function and up-regulate their NCAM expression. High-dose TPM could reduce epilepsy rats＇ cognitive function and inhibit their NCAM expression, and those effects of highdose TPM were time-related.