局灶性脑缺血再灌注致大鼠大脑皮质tau蛋白异常高度磷酸化  

Tau Protein Phosphorylation Induced by Focal Cerebral Ischemia-reperfusion in Rat Parietal Cortex Neurons

作　　者：王海均[1] 赵洪洋[1] 熊南翔[1] 黄俊红[1] 姚东晓[1] 赵心同[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经外科,武汉430022

出　　处：《华中科技大学学报（医学版）》2009年第6期739-743,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家"十一五"科技支撑课题资助项目(No.2006BAI01A13)

摘　　要：目的探讨局灶性脑缺血再灌注后大鼠顶叶皮质神经元tau蛋白磷酸化的变化,及其与神经细胞凋亡的关系,以阐明脑梗死和阿尔茨海默病间的关系。方法制作局灶性脑缺血再灌注模型,应用免疫印迹法检测局灶性脑缺血再灌注后大鼠顶叶皮质tau蛋白在Ser199/202、Ser396、Ser404和Tyr231位点磷酸化和不溶性磷酸化tau蛋白的变化;TUNEL法和免疫荧光双标法检测脑缺血再灌注后神经细胞凋亡和磷酸化tau蛋白的关系。结果缺血再灌注6 h后顶叶皮质tau蛋白在Ser199/202、Ser396、Ser404和Tyr231位点发生异常高度磷酸化,不溶性磷酸化tau蛋白显著增加。脑缺血再灌注后3 d神经细胞的凋亡和tau蛋白高度磷酸化呈显著正相关关系。结论脑缺血再灌注后发生阿尔茨海默病样病理变化,脑梗死可能促进了阿尔茨海默病的发生、发展。Objective To explore the changes of tau protein phosphorylation in rat parietal cortex neurons after focal cerebral ischemia-reperfusion（I/R）and to clarify the relationship between cerebral infarction and Alzheimer＇s disease.Methods The rat focal cerebral I/R model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method.The level of tau hyperphosphorylation at Ser199/202,Ser396,Ser404 and Tyr231 sites and total tau in rat parietal cortex during focal cerebral I/R was detected by immunofluorescence and Western blot.The relationship between neuronal apoptosis and tau protein phosphorylation was analyzed by TUNEL method and immunofluorescence.Results The levels of tau hyperphosphorylation at Ser199/202,Ser396,Ser404 and Tyr 231 sites were significantly higher in I/R group than those in the sham group,but the total tau was not increased.Neuronal apoptosis and the tau protein hyperphosphorylation were co-localized.Conclusion The cerebral infarction may contribute to Alzheimer＇s disease occurrence and development.

关 键 词：脑缺血 阿尔茨海默病 TAU蛋白 磷酸化 细胞凋亡 

分 类 号：R364.12[医药卫生—病理学]