Wang Haijun, Zhao Hongyang, Ye Youfan, Xiong Nanxiang, Huang Junhong, Yao Dongxiao, Shen Yin, Zhao Xintong
Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
J Huazhong Univ Sci Technolog Med Sci. 2010 Feb;30(1):29-36. doi: 10.1007/s11596-010-0106-4. Epub 2010 Feb 14.
The changes in the tau protein phosphorylation and expression of bcl-2, and bax in rat parietal cortex neurons after focal cerebral ischemia-reperfusion (I/R) were explored, and the relationship between the tau protein phosphorylation and the expression of bax or apoptosis was clarified in order to elucidate the relationship between cerebral infarction and Alzheimer's disease. 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 protein phosphorylation at Ser396, Ser404, Tyr231, Ser199/202 sites and the expression of bcl-2, bax and total tau 5 in rat parietal cortex during focal cerebral ischemia/reperfusion were detected by Western blot. The relationship between the tau protein phosphorylation and the expression of bax, or apoptosis was examined by TUNEL method and double-labeling immunofluorenscence method. The results showed that the level of tau hyperphosphorylation at Ser199 / 202, Ser396, Ser404, Tyr231 sites and the expression levels of bcl-2, and bax were significantly higher in I/R group than in the sham group, but the ratio of bcl-2/bax was decreased. Neuronal apoptosis, bax expression and the tau protein hyperphosphorylation were co-localized. It is suggested that Alzheimer's disease-like pathological changes occur after cerebral I/R. The highly abnormal phosphorylation of tau protein plays a key role in cerebral I/R-induced apoptosis. The cerebral infarction may contribute to Alzheimer's disease occurrence and development.
探讨局灶性脑缺血再灌注（I/R）后大鼠顶叶皮质神经元tau蛋白磷酸化及bcl-2、bax表达的变化，阐明tau蛋白磷酸化与bax表达或细胞凋亡之间的关系，以揭示脑梗死与阿尔茨海默病之间的联系。采用管腔内缝合线法阻断大鼠右侧大脑中动脉，建立局灶性脑I/R模型。采用蛋白质免疫印迹法检测局灶性脑缺血/再灌注期间大鼠顶叶皮质中Ser396、Ser404、Tyr231、Ser199/202位点的tau蛋白磷酸化水平以及bcl-2、bax和总tau 5的表达。采用TUNEL法和双标免疫荧光法检测tau蛋白磷酸化与bax表达或细胞凋亡之间的关系。结果显示，I/R组Ser199/202、Ser396、Ser404、Tyr231位点的tau蛋白过度磷酸化水平以及bcl-2和bax的表达水平均显著高于假手术组，但bcl-2/bax比值降低。神经元凋亡、bax表达与tau蛋白过度磷酸化共定位。提示脑I/R后可出现类似阿尔茨海默病的病理改变。tau蛋白高度异常磷酸化在脑I/R诱导的细胞凋亡中起关键作用。脑梗死可能促使阿尔茨海默病的发生和发展。
