匹罗卡品致癫痫小鼠海马中精神分裂症断裂基因1蛋白的表达及其在癫痫中的作用

Expression of disrupted-in-schizophrenia 1 in the hippocampus of epileptic mice induced by pilocarpine and its effect on epilepsy

目的：研究精神分裂症断裂基因1（DISC1）蛋白及其mRNA在匹罗卡品致癫痫小鼠海马中的表达变化，探讨其在癫痫发病过程中的作用。方法将246只雄性C57 BL／6（3～4周）小鼠随机分为实验组（198只）和对照组（48只），实验组采用匹罗卡品小剂量给药方法建立癫痫小鼠模型。采用免疫组化和Real－Time PCR定性、定量分析方法分别于癫痫持续状态后3 d，7 d，14 d，28 d检测实验组和对照组小鼠海马组织中DISC1和微小染色体维持蛋白2（MCM2）的表达改变。结果与对照组相比，实验组小鼠齿状回各时间点MCM2阳性细胞数目和MCM mRNA明显增加（P＜0．05～0．01），随着时间增加，对照组这两者均明显下降（均P＜0．05）。自第7 d开始，实验组各时间点的海马齿状回和CA3区DISC1蛋白及DISC1 mRNA表达显著低于对照组（P＜0．05～0．01）。 Pearson相关性分析发现DISC1和MCM2的表达水平呈显著相关（P＜0．01）。结论 DISC1可能通过介导癫痫后新生神经元增生参与癫痫发生过程。

Objective To studied the protein and mRNA level of the disrupted-in-schizophrenia 1 （ DISC1 ） in the hippocampus of epileptic mice induced by pilocarpine and its effect on epilepsy .Methods Two hundreds and six male C57BL/6 mice were randomly diveded into experimental group （n=198） and control group （n=48）,the mice in experimental group were given small dosage of pilocarpine to set up the epileptic mice model .Expression of DISC1 and minichromosome maintenance protein 2 （ MCM2 ） in the hippocampus of two groups were analysed via immunohistochemistry and real-time PCR at different time points （3,7,14,28 d） after status epilepticus.Results Compared with the control group ,the quantity of MCM2 posotive cells and MCM2 mRNA in experimental group were significant increased at each time point （P〈0.05-0.01）, which appeared a decreasing tendency in control group （all P〈0.05）.Compared with the control group, the expression level of DISC1 and DISC1 mRNA at dentate gyrus and CA3 area in experimental group were significantly lower from 7 d（P〈0.05-0.01）.A significant correlation existed between the expression level of DISC 1 and MCM2 according to Pearson correlation analysis （ P〈0.01 ） .Conclusion DISC1 may participate in the pathogenesis of epilepsy by mediating the proliferation of new neurons .