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作 者:张萌琦[1] 丁慧 李蜀渝[1] 李国良[1] 卢晓琴[1] 毕方方[1] 肖波[1] 刘卫平[1] ZHANG Meng-qi;DING Hui;LI Shu-yu(Department of Neurology,the Xiangya Hospital,Central Southern University,Changsha 410008,China)
机构地区:[1]中南大学湘雅医院神经内科,湖南长沙410008
出 处:《医学临床研究》2018年第12期2293-2296,2300,共5页Journal of Clinical Research
基 金:国家自然科学基金(81501025);湖南省自然科学基金(2016JJ3174);湖南省发改委基金[2011]1318.
摘 要:【目的】探讨匹罗卡品致痫大鼠海马CA1区EphA4、ephrinA3的表达变化及其意义。【方法】采用匹罗卡品建立颞叶癫痫SD大鼠模型;以免疫组织化学和原位杂交法分别检测致痫后不同时间点海马CA1区EphA4蛋白和ephrinA3基因变化;快速Golgi染色观察CA1区树突棘的形态学改变;共聚焦显微镜观察ephrinA3在星形胶质细胞的动态变化。【结果】颞叶癫痫大鼠海马CA1区EphA4及 ephrinA3有高表达;与对照组比较;致痫后7 d;EphA4蛋白、ephrinA3 mRNA的表达下调;降至最低点(P<0.01);此后逐渐回升;但15 d时仍低于对照组(P<0.05);30 d和60 d时回归至对照组水平(P>0.05);致痫后7 d;CA1区锥体细胞树突棘变细、变长;而且密度增高;ephrinA3在成熟鼠海马的星形胶质细胞表达;致痫后7 d;ephrinA3在大鼠海马的星形胶质细胞表达明显下调;癫痫持续状态后15 d有所回升;但仍然低于对照组。30 d恢复正常。【结论】EphA4 蛋白、ephrinA3 mRNA在CA1的表达下调参与了突触后树突棘形态的调节;是调节突触可塑性的重要分子之一。【Objective】 To investigate the changes and significance of EphA4,ephrinA3 expression in hippocampal CA1 region of epileptic rats induced by pilocarpine.【Methods】 The SD rat model of temporal lobe epilepsy was established by pilocarpine. The changes of EphA4 protein and ephrinA3 gene in hippocampal CA1 at different time points were detected by immunohistochemistry and in situ hybridization.The morphological changes of dendritic spine in CA1 region were observed by rapid Golgi staining and the dynamic changes of ephrinA3 in astrocytes were observed by confocal microscopy.【Results】 The expression of EphA4 and ephrinA3 in hippocampal CA1 was high in temporal lobe epilepsy rats. Compared with the control group, the expression of EphA4 protein and ephrinA3 mRNA decreased to the lowest point at 7 days after epilepsy (P<0.01). After that, it increased gradually, but it was still lower than the control group at 15 days (P<0.05), and returned to that of the control group at 30 and 60 days (P>0.05). The dendritic spine of pyramidal cells in CA1 area became thinner, longer and denser at 7 days after epilepsy. EphrinA3 was expressed in the astrocytes of the hippocampus of the mature rats. The expression of ephrinA3 in the astrocytes of the hippocampus of the rats was down-regulated 7 days after epilepsy, and increased at 15 days after epileptic status, but it was still lower than that of the control group and returned to normal at 30 days.【Conclusion】 The down-regulation of the expression of EphA4 protein and ephrinA3 mRNA in CA1 participates in the regulation of postsynaptic dendritic spine morphology and is one of the important molecules regulating synaptic plasticity.
关 键 词:大鼠 Sprague-Dawley/畸形 药用制剂 蛋白质类
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