戊四氮致痫大鼠海马GSK-3β表达与苔藓纤维出芽关系研究  

Study on the relationship between GSK-3β expression and mossy fiber sprouting in hippocampus of rats kindled by PTZ

作　　者：陈金梅[1] 田发发[2] 郭婷辉[2] 马云峰[2] 

机构地区：[1]上海市普陀区人民医院神经内科,上海200060 [2]中南大学湘雅医院神经内科,湖南长沙410008

出　　处：《中风与神经疾病杂志》2008年第5期516-519,共4页Journal of Apoplexy and Nervous Diseases

基　　金：湖南省教育厅资助项目(湘财教[2004]29号;[2006]26号)

摘　　要：目的观察戊四氮（PTZ）致痫大鼠海马各区糖原合成酶激酶-3β（GSK-3β）蛋白及其mRNA表达和苔藓纤维出芽（MFS）情况,探讨GSK-3β在癫痫发病机制中的作用。方法SD雄性成年大鼠120只,随机分为实验组和对照组;实验组分为PTZ第1次注射后3d、1w、2w、4w、6w共5个亚组,每亚组12只。对照组同样随机分为5个亚组,每亚组12只,与实验组各时间点对应。以上各亚组再分2个小组,每小组6只大鼠,分别进行（1）GSK-3β的免疫组化和原位杂交染色并测定其相应的光密度值;（2）Timm染色并评分。结果实验组大鼠海马各区GSK-3β蛋白及其mRNA表达在点燃过程中逐渐增多,点燃后表达逐渐下调到正常对照组水平,在点燃前后除6w组外GSK-3β表达与对照组相应时间点比较差异有统计学意义（P〈0.05）;实验组CA3区在点燃前可见1-4级MFS,点燃后可见4-5级MFS;癫痫点燃过程中CA3区GSK-3β表达与MFS评分有线性正相关关系。结论GSK-3β在海马表达变化可能在苔藓纤维出芽的过程中起促进作用,从而促进癫痫的发生。Objective To investigate the expression of Glycogen synthase kinase-3β changed in pentetrazole kindling epileptic rat hippocampus and the relationship between the expression of Glycogen synthase kinase-3β and mossy fiber sprouting. Methods 120 healthy male SD rats were divided randomly into normal controls and epileptic groups. The mod- els of epilepsy were established by injection of pentetrazole intraperitoneally. At 3d, 1 w,2w,4w and 6w after daily injection of pentetrazole, the GSK-3 βprotein ,mRNA and mossy fiber sprouting were analyzed at different time quantitatively in CA1 , CA3 regions and dentate gyrus of hippocampus, by using immunohistochemistry, in situ hybridization and Timm staining. Results There was a gradually increase of GSK-3β levels measured at 3d,1w,2w and decreased slowly to normal level at 4w,6w after pentetrazole administration,which had a noticeable difference as compared with corresponding time of control groups except 6w（P 〈 0.05 ）. Timm＇ s scoree for epilepsy groups was 1 - 4 grade before kindling kindling and 4 - 5 grade after kindling in CA3 regions. The relationship during kindling procession between the expression of GSK-3 β and the score of MFS in CA3 region was linear positive correlation. Conelusion The change of GSK-3β expression in hippocampus might advance the procession of mossy fiber sprouting and accordingly epilepsy occurred.

关 键 词：戊四氮 癫痫模型 糖原合成酶激酶-3Β 苔藓纤维出芽 

分 类 号：R742.1[医药卫生—神经病学与精神病学]