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目的探讨匹罗卡品致痫小鼠自发性癫痫发作(SS)模型的特点,并观察癫痫发作后其齿状回颗粒细胞下层新生神经细胞(NPC)增生变化。方法建立SS小鼠模型,进行行为学检测。将SS发作小鼠在癫痫持续状态(SE)后不同时间点进行Doublecortin(DCX)免疫组化,Western blot观察海马NPC的分布和表达改变。结果 80%的模型小鼠出现持续SS,发作时程约10～40 s,发作频率为2.18±0.45次/周。DCX+细胞及其蛋白表达在模型组中显著增多(P<0.05),SE后4周最为明显,SE后8周开始下降,至SE后12周显著减少。增生的DCX+细胞呈簇状分布,随时间推移出现迁移分散。存在SS的模型小鼠相对于不存在SS的模型小鼠DCX+细胞增生更为明显。结论匹罗卡品致痫后SS小鼠模型存在持续的NPC增生,这可能在慢性期癫痫持续发作的病理生理机制中有着重要作用。
Objective To investigate the characteristics of spontaneous epileptic seizures (SS) model of epileptic mice induced by pilocarpine and observe the proliferation of neonate neurons (NPC) in the dentate gyrus after epileptic seizures. Methods SS mouse model was established for behavioral testing. The SSc mice were immunostained with Doublecortin (DCX) at different time points after SE, and the distribution and expression of NPC were observed by Western blot. RESULTS: Eighty percent of the model mice developed persistent SS with a duration of 10 to 40 seconds and a frequency of 2.18 ± 0.45 beats / week. The expression of DCX + cells and their proteins increased significantly in the model group (P <0.05). The expression of DCX + cells in the model group was most obvious at 4 weeks after SE. The levels of DCX + cells began to decline at 8 weeks and decreased significantly at 12 weeks after SE. Proliferation of DCX + cells were clustered and migrated over time. DCX + cell proliferation in model mice with SS is more pronounced than model mice without SS. Conclusions There is persistent NPC hyperplasia in SS mouse model induced by pilocarpine, which may play an important role in the pathophysiology of chronic epilepsy.