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目的观察水通道蛋白AQP4mRNA和其蛋白在颞叶癫大鼠海马表达的时空变化,探讨其在癫发生发展中的作用。方法采用氯化锂匹罗卡品致大鼠模型,运用原位杂交和免疫组化检测不同时间点大鼠海马齿状回(DG区)、CA1、CA3区AQP4mRNA和其蛋白表达。结果AQP4mRNA和其蛋白表达主要在CA1、CA3区的锥体细胞和DG区的颗粒细胞;致后6～24h海马各区AQP4mRNA表达显著增加,差异具有显著性意义(P<0.01),蛋白表达从12h开始显著增加,24h到达高峰;静止期各区AQP4表达逐渐下降至正常水平,慢性自发发作期DG区AQP4mRNA和其蛋白表达再次显著增加(P<0.01)。结论性发作后急慢性期海马AQP4表达增加,AQP4表达增加可能增加海马神经元兴奋性,导致性发作加剧的恶性循环;DG区颗粒细胞AQP4表达改变在癫发生发展中的作用可能较CA1、CA3区更重要。
Objective To observe the temporal and spatial changes of aquaporin AQP4 mRNA and its protein expression in the hippocampus of temporal lobe epilepsy rats and its role in the development of epilepsy. Methods Rat model was induced by lithium pilocarpine. The expression of AQP4 mRNA and protein in hippocampal dentate gyrus (DG) area, CA1 and CA3 area were detected by in situ hybridization and immunohistochemistry at different time points. Results The expression of AQP4 mRNA and protein were mainly in pyramidal cells of CA1 and CA3 and granulosa cells in DG area. The expression of AQP4 mRNA in hippocampus significantly increased at 6 ~ 24 h after CLP (P <0.01) The expression of AQP4 gradually decreased to the normal level in all regions in quiescent phase. The expression of AQP4 mRNA and protein in DG zone increased again (P <0.01) after chronic spontaneous onset. CONCLUSIONS: AQP4 expression is increased in acute and chronic hippocampus after acute seizure, and the increase of AQP4 may increase the excitability of hippocampal neurons, resulting in a vicious cycle of seizures. The change of AQP4 expression in DG may play an important role in the development of epilepsy CA1, CA3 area is more important.