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 |
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引用本文: | 王海均,赵洪洋,熊南翔,黄俊红,姚东晓,赵心同. 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[J]. 华中科技大学学报(医学版), 2009, 38(6). DOI: 10.3870/j.issn.1672-0741.2009.06.005 |
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作者姓名: | 王海均 赵洪洋 熊南翔 黄俊红 姚东晓 赵心同 |
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作者单位: | 华中科技大学同济医学院附属协和医院神经外科,武汉,430022 |
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基金项目: | 国家"十一五"科技支撑课题资助项目 |
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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Serl99/202、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.
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关 键 词: | 脑缺血 阿尔茨海默病 tau蛋白 磷酸化 细胞凋亡 |
Tau Protein Phosphorylation Induced by Focal Cerebral Ischemia-reperfusion in Rat Parietal Cortex Neurons |
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Abstract: | 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 immunofluoreseenee and Western blot.The relationship between neuronal apopto-sis 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. |
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Keywords: | cerebral ischemia Alzheimer's disease tau protein phosphorylation apoptosis |
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