罗非昔布对阿尔茨海默病模型小鼠脑内tau蛋白表达的影响  

Effect of rofecoxib on tau protein expression in brain of transgenic mice with Alzheimer＇s disease

作　　者：王玥[1] 于嵩[1] 王旭[1] 王淳[1] 

机构地区：[1]辽宁中医药大学解剖组胚教研室,沈阳110847

出　　处：《中华行为医学与脑科学杂志》2016年第10期887-890,共4页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：辽宁省自然科学基金项目（2015020379）

摘　　要：目的研究罗非昔布对tau转基因小鼠脑内磷酸化tau蛋白表达的影响0方法实验小鼠分为对照组、AD模型组和罗非昔布治疗组，治疗组小鼠给予罗非昔布（2mg·kg^-1·d^-1）饮水喂养处理6个月，对照组和模型组均给予正常饮用水。应用水迷宫实验方法检测三组小鼠的学习记忆能力；并应用免疫荧光和Western blot等实验方法检测磷酸化tau蛋白在三组小鼠脑内的表达情况。结果Westemblot和免疫荧光结果显示AD模型小鼠脑内的tau蛋白磷酸化水平在Ser202和Ser404两个位点明显高于野生型小鼠，经罗非昔布干预6个月后，tau蛋白磷酸化水平较模型组降低；行为学实验结果提示罗非昔布治疗组小鼠在第3和第4天的平均潜伏期分别为（44．45±2．40）s和（36．7±3．09）s，搜索的平均路程分别为（1．55±0．17）m和（1．45±0．15）m，显著低于模型组小鼠的潜伏期和搜索的平均路程。结论罗非昔布能够降低AD小鼠脑内的tau蛋白磷酸化水平，进而改善其学习记忆能力，提示罗非昔布在AD的临床治疗方面具有重要的理论意义。Objective To investigate the effect on phosphorylated tau protein expression in the tau transgenic mice brain. Methods The mice were divided into three groups, namely the wild type group, the AD model group and the treatment group. As for the treatment group, the mice were given rofeeoxib （ 2 mg·kg^-1·d^-1） treatment for 6 months, and the wild type group and the model group were given normal drinking water. Learning and memory function was assayed by Morris water maze, and Western blot and im- munofluorescence were used to detect the expression of phosphorylated tau protein in the brain of the three groups of mice. Results Western blot and immunofluorescence results showed that the phosphorylation level of tan protein in the brain of AD model mice was significantly higher than that of wild-type mice at site Ser202 and site Ser404.Mter the intervening with rofecoxib for 6 months,tau protein phosphorylation was reduced; Behavioral results indicated that the average incubation periods of rofecoxib treated mice in the third and fourth days were （44.45±2.40） s and （36.70±3.09） s,the average search journey were （1.55±0.17） m and （1.45±0.15）re,which were significantly lower than that in the model group mice,indicating that the mice learning memory ability was improved obviously. Conclusion Rofecoxib can decrease the level of tau phosphorylation in the brain of AD mice and improve the learning and memory ability. It suggests that rofe- coxib has important theoretical significance.

关 键 词：罗非昔布 TAU蛋白磷酸化 tau转基因小鼠 学习记忆 

分 类 号：R749.16[医药卫生—神经病学与精神病学]