丙戊酸钠对APPPS1双重转基因小鼠脑组织Tau蛋白的影响.doc

丙戊酸钠对APP/PS1双重转基因小鼠脑组织Tau蛋白的影响 赵蕾1 龙志敏1 贺桂琼1,2,* 宋冲1楚亚楠1　 1神经生物学重庆市重点实验室 2解剖教研室 重庆医科大学 重庆 400016 [摘 要]：探讨丙戊酸钠（Valproic acid, VPA）对APP/PS1双转基因阿尔茨海默病(Alzheimer’s disease, AD)模型小鼠丝氨酸262位点Tau蛋白过度磷酸化（p-tau-ser262）及神经细胞内神经原纤维缠结(neurofibrillary tangles, NFTs)的影响。方法：3月龄APP/PS1双重转基因AD模型小鼠20只，随机均分为VPA治疗组和生理盐水对照组（每组10只）。腹腔注射VPA和等量生理盐水4周后取材，应用免疫组化方法检测各组AD模型鼠脑内p-tau-ser262阳性细胞表达，H.E.染色显示NFTs的数量及分布变化；western blot 分析各组AD模型鼠脑内GSK-3β蛋白ser9位点磷酸化水平。结果：免疫组化结果：与生理盐水对照组相比，VPA治疗组AD模型小鼠皮质、海马、嗅球、小脑P-tau-ser262阳性细胞数明显减少(P)；H.E.染色结果显示：对照组VPA治疗组海马和区NFTs数量降低(P0.01)；western blot结果VPA治疗AD模型鼠脑内GSK-3β蛋白ser9磷酸化水平明显高于生理盐水对照组(P)。结论：VPA可明显减少AD模型小鼠脑内tau蛋白的过度磷酸化及NFTs的形成；VPAGSK-3β活性【关键词】 丙戊酸钠；阿尔茨海默病；神经原纤维缠结；【中图分类号】【文献标识码】 The effect of valproic acid on tau in the brain of APP/PS1 double transgenic mouse model. Zhao Lei1, Long Zhi-min1, He Gui-qiong1,2,*,Song Chong1, Chu Ya-lan1 1 Chongqing Key Laboratory of neurobiology, 2 Department of Anatomy, Chongqing Medical University, Chongqing, 400016, China 【Abstract】 Objective　To investigate the effect of valproic acid (VPA) on the expression of hyperphosphorylated-tau (p-tau-ser262) and neurofibrillary tangles (NFTs) in the brain of APP/PS1 double transgenic mouse model. Methods　APP/PS1 transgenic mice at the age of 3 months were randomly divided into saline-treated control group and VPA treated group (10 in each group).VPA treated group and control mice were intraperitoneally (i.p.) injected with VPA or same amount of saline once a day for 4 weeks. Immunohistochemical staining and H.E. staining were used to detect the expression of p-tau-ser262 and NFTs in the brain of AD mice; the p-GSK-3β-ser9 protein level in brain of AD model mouse were analyzed by western blot. Results Immuohistochemical staining showed that the number of p-tau-ser262 positive cells was significantly lower in the cerebral cortex, hippocampus, basal nuclei, olfactory bulb and cerebellum of VPA-treated mice(P0.05); H.E. staining revealed that the number of NFTs was significantly decreas