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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 investigate the effect of topiramate (TPM) on cognitive function in epileptic rats and the change of mRNA expression of neural cell adhesion molecule (NCAM) in hippocampus of rats after using TPM. Methods The rats were randomly divided into NS group, epileptic group (EP), epilepsy plus topiramate (TPM) for one week (TPM for one week) and epilepsy plus topiramate for four weeks (TPM for four weeks) Induced epilepsy rats model and TPM intervention model. The behavioral changes of rats were observed. Morris water maze test was used to evaluate the learning and memory ability of rats. NCAM mRNA expression in hippocampus was detected by Real-Time PCR. Results The escape latency of rats in EP group was greater than that of NS group. The percentage of swimming time in quadrant of original platform was smaller than that in NS group. NCAM mRNA expression in hippocampus was higher than that in NS group (P <0.01) (P <0.01). The escape latency of rats in TPM4-week group was larger than that of TPM1-week group, and the percentage of swimming time in quadrant of original platform was less than that in EP group and hippocampus The mRNA expression of NCAM in the TPM1 week group and hippocampus was lower than that in the TPM1 week group (P <0.05). CONCLUSION: Cognitive function in rats with persistent status epilepticus is significantly decreased and the mRNA expression of NCAM in the hippocampus is increased. After short-term treatment with high-dose TPM, the cognitive function is further decreased and the mRNA expression of NCAM in the hippocampus is inhibited. And TPM continuous use of time.