盐酸美金刚对癫痫大鼠海马GSK-3β表达的影响

The effect of memantine on the expression of glycogen synthase kinase-3β in hippocampus of epileptic rats

目的探讨盐酸美金刚(memantine,MN)对戊四氮(pentylenetetrazol,PTZ)点燃慢性癫痫大鼠学习记忆能力及海马中糖原激酶合酶-3β(glycogen synthase kinase-3,GSK-3β)表达的影响。方法动物分为正常对照组(NC)、癫痫组(PTZ)、盐酸美金刚干预组(MN),采用PTZ致痫模型,Morris水迷宫检测各组大鼠空间学习记忆能力,Western blot和RT-PCR方法检测大鼠海马GSK-3β、P-GSK-3β蛋白和GSK-3βmRNA表达。结果 PTZ组大鼠空间学习记忆能力受损,其海马中P-GSK-3β蛋白表达明显减少(P<0.05),GSK-3β蛋白和mRNA表达无变化(P>0.05)。MN组大鼠学习记忆能力明显好转,其海马中P-GSK-3β蛋白表达明显升高(P<0.05),GSK-3β蛋白和mRNA表达无变化(P>0.05)。结论 PTZ点燃慢性癫痫大鼠学习记忆受损,其海马组织中P-GSK-3β蛋白表达明显降低,P-GSK-3β可能参与癫痫后认知功能障碍发病机制;盐酸美金刚可提高P-GSK-3β蛋白表达水平,从而改善癫痫大鼠学习记忆能力。

Objective To explore the effect of memantine（MN） on learning and memory,the protein and mRNA expression of glycogen synthase kinase-3 in the hippocampus of chronic epileptic rats kindled by pentylenetetrazol（PTZ）.Methods Adult male SD rats were selected through Y-Maze tests and then divided into normal control group,PTZ group and MN group.All of the rats were tested with Morris water maze to assess the ability of the learning and memory,and the expression of GSK-3β,P-GSK-3β proteins and GSK-3β mRNA was determined by Western Blot and RT-PCR.Results The ability of learning and memory in rats of PTZ group was impaired and the expression of P-GSK-3β protein in hippocampus decreased obviously compared to NC group（P0.05）.Comparisons of GSK-3β protein and mRNA between NC group and PTZ group were of no significant difference（P0.05）.The learning and memory ability of rats in MN group improved significantly and P-GSK-3β protein increased obviously compared with that in PTZ group（P0.05）.The expression of GSK-3β protein and mRNA had no changes.Conclusions The ability of learning and memory in PTZ-kindled chronic epilepsy rats was impaired.The expression of P-GSK-3β protein in the hippocampus of epilepsy rats was decreased.GSK-3β might participate in the mechanism of impaired cognition after epilepsy.Memantine can increase the expression level of P-GSK-3β protein,thus improves the impaired cognitive function of epileptic rats.