构建海人酸诱导的内侧颞叶癫痫小鼠模型  

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

作　　者：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] 

机构地区：[1]中国医学科学院北京协和医学院基础医学研究所基础学院生物化学与分子生物学系,北京100005 [2]中国医学科学院北京协和医学院北京协和医院,北京100730

出　　处：《基础医学与临床》2011年第7期820-826,共7页Basic and Clinical Medicine

基　　金：国家自然科学基金(30971001;30721063);北京自然科学基金(7102109);霍英东教育基金(121024)

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、0.9%氯化钠注射组(35μL/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。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（HE） 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（P0.05） and chronic phases（P0.01） of MTLE models.Conclusion Intrahippocampal injection of KA inC57BL/6 mice could induce behavioural,histopathological changes which are similar to those clinic features of MTLE.

关 键 词：内侧颞叶癫痫 海人酸 C57BL/6小鼠 海马硬化 

分 类 号：R742.1[医药卫生—神经病学与精神病学]