不同剂量托吡酯对癫痫大鼠认知功能的影响

The effects of different doses of topiramate on rats' cognitive function in rat epilepsy models induced by kainic acid

目的探讨不同剂量托吡酯对颞叶癫痫大鼠学习、记忆等认知功能影响。方法 48只健康雄性SD大鼠,随机分为5组,正常对照组(第1组)8只、癫痫对照组(第2组)10只、托吡酯20 mg/kg治疗组(第3组)10只、托吡酯40 mg/kg治疗组(第4组)10只、托吡酯80 mg/kg治疗组(第5组)10只。利用立体定位仪向大鼠右侧海马CA3区注射海人酸致痫,灌胃6周后,行Morris水迷宫测试,监测大鼠记忆功能。结果在4 d的训练中,第2组每天寻找平台的时间长于第1组,次数少于第1组,差异有统计学意义(P<0.05);第4、5组每天寻找平台时间均长于第2组,次数少于第2组,差异有统计学意义(P<0.05);第3组与第2组比较差异无统计学意义(P>0.05)。结论 托吡酯对癫痫大鼠认知功能的影响与剂量有关,低剂量的托吡酯对认知功能无明显影响,中剂量和大剂量的托吡酯使大鼠认知功能下降。

Objective To investigate the effect of different doses of topiramate on rats＇ cognitive function in rats with epilepsy induced by Kainic acid.Methods 48 health male Sprague-Dawley rats,weighted（100±10g）,were randomly divided into 5 groups：normal control group（n=8）,epilepsy model group（n=10）,low-dose topiramate（20mg/kg） treatment group（n=10）,medium-dose topiramate（40mg/kg） treatment group（n=10）,high-dose topiramate（80mg/kg） treatment group（n=10）.The rat epilepsy models were established by using stereotaxic apparatus to inject kainic acid into CA3 zone of right-side hippocampus,after 6-week gavage,the Morris water maze test was conducted to evaluate the rats＇ memory function.Results During the 4-day trainning,the average time of looking for the platform everyday in epilepsy model group was significantly longer than that of normal control group,however,the number of times of looking for the platform in epilepsy model group was significantly fewer than that in normal control group（P0.05）.The average time of looking for the platform everyday in medium-dose and high-dose topiramate treatment groups was significantly longer than that of epilepsy model group,however,the number of times of looking for the platform in the two groups was significantly fewer than that of epilepsy model group,and there was a significant difference between medium-dose topiramate treatment group and epilepsy model group,and between high-dose topiramate treatment group and epilepsy model group（P0.05）.However there was no significant differennce between low-dose topiramate treatment group and epilepsy model group（P0.05）.Conclusion The effects of topiramate on rats＇ cognitive functions are dose-dependment.The low-dose topiramate has no obvious effect on the rats＇ cognitive function,but medium-dose and high-doae topiramate can reduce the rats＇ cognitive function.