基础医学与临床 ›› 2011, Vol. 31 ›› Issue (7): 820-826.

• 研究论文 • 上一篇    下一篇

构建海人酸诱导的内侧颞叶癫痫小鼠模型

何婷婷1,张丹2,幸小亮1,沙龙泽1,金丽日2,沈岩1,吴立文2,许琪1   

  1. 1. 中国医学科学院基础医学研究所
    2. 北京协和医院
  • 收稿日期:2011-05-13 修回日期:2011-05-16 出版日期:2011-07-05 发布日期:2011-07-05
  • 通讯作者: 许琪 E-mail:qixu@vip.sina.com
  • 基金资助:
    国家自然科学基金;北京自然科学基金;霍英东教育基金

Establishment of kainic acid-induced mice models of medial temporal lobe epilepsy

Ting-ting HE1,Dan ZHANG2,Xiao-liang XING2,Long-ze SHA2,Li-ri JIN2,Yan SHEN2,Li-wen WU2,Qi XU1   

  1. 1. Institute of Basic Medical Sciences, CAMS & PUMC
    2.
  • Received:2011-05-13 Revised:2011-05-16 Online:2011-07-05 Published:2011-07-05
  • Contact: Qi XU E-mail:qixu@vip.sina.com

摘要: 目的 建立C57BL/6颞叶癫痫小鼠模型,观察其在行为学和病理学上的变化。 方法 将C57BL/6小鼠随机分为空白对照组、生理盐水注射组(35 μL/g)和海人酸注射组(12 mg/kg),进行单侧海马注射。注射5 d或5周后,取小鼠脑进行HE染色,观察海马病理结构改变;检测海马组织中mTOR通路标志物P-S6蛋白质表达量的改变。结果(1)海人酸注射小鼠发生面部抽搐、双侧前肢痉挛等急性期癫痫持续发作和慢性期自发发作;(2)海马注射侧CA1、CA3神经元明显丢失,慢性期小鼠模型出现中齿状回颗粒细胞散布,符合海马硬化特征性病理改变;(3)小鼠海马组织中P-S6蛋白质的表达量在急性期(P < 0.05)和慢性期(P < 0.01)均上调。结论 单侧海马注射海人酸可成功建立C57BL/6小鼠内侧颞叶癫痫模型,可观察到与内侧颞叶癫痫临床表现类似的行为学、组织病理学上的改变。

关键词: 内侧颞叶癫痫, 海人酸, C57BL/6小鼠, 海马硬化

Abstract: Objective To establish the kainic acid (KA)-induced mesial temporal lobe epilepsy (TLE) mice model and detect the characteristic changes. Methods Healthy male C57BL/6 mice were randomly divided into control group (non-injected), saline group (35 μL/g) and KA group (12 mg/kg) for intrahippocampal injections. 5 days and 5 weeks after injection,the mice brains were sectioned and stained by hemotoxylin-eosin (H&E) to detect the pathologic changes in the hippocampal area; the expression level of P-S6 protein, the marker of hippocampus mTOR signal pathway, was also determinated to verify the animal model. Results (1)Only KA-treated mice showed wet dog shakes, facial clonus and generalized tonic-clonic convulsions.(2)After injection of KA, neuronal cell loss was prominent in in CA1, CA3 and hilar area of the ipsilateral hippocampus; granule cell in dentate gyrus area dispersed, which are fertures of hippocampus sclerosis.(3)P-S6 expression level increased in both acute (P < 0.05) and chronic phases (P < 0.01) of MTLE models. Conclusion Intrahippocampal injection of KA in C57BL/6 mice could induce behavioural, histopathological changes which are similar to those clinic features of MTLE.

Key words: mesial temporal lobe epilepsy, kainic acid, C57BL/6 mice, hippocampus sclerosis