罗格列酮对三重转基因小鼠认知障碍的干预作用  

Rosiglitazone improves learning and memory impairment of 3×Tg mice

作　　者：宋金芝[1] 孙洁[1] 金多晨 邓艳秋[1] 

机构地区：[1]天津医科大学基础医学院,天津300070

出　　处：《药学学报》2014年第6期807-812,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30973156;81270422)

摘　　要：观察胰岛素增敏剂罗格列酮对3×Tg小鼠认知障碍的影响。以雄性C57/BL6小鼠分为正常对照组(WT组)和药物干预组(RSG组),取雄性APP/PS1/tau转基因小鼠随机分为模型组(3×Tg模型组)和罗格列酮治疗组(3×Tg+RSG治疗组)。6月龄小鼠成模后,3×Tg+RSG组和RSG组给予罗格列酮(2.5 mg·kg-1·d-1)灌胃治疗8周,其他组给予等量生理盐水;选用Morris水迷宫实验评估小鼠的认知功能,采用蛋白免疫印迹技术检测小鼠脑内细胞Tau蛋白和NFs蛋白磷酸化水平及糖基化水平。结果显示:与WT组和RSG组相比,3×Tg模型组的逃避潜伏期和路径长度显著增加,同时明显减少平台所在象限的停留时间和穿越隐匿平台的次数(P<0.05);此外,模型小鼠脑内Tau蛋白和NFs蛋白磷酸化表达水平明显增高而糖基化相关蛋白的表达显著降低(P<0.05);但3×Tg+RSG治疗组在上述行为学和细胞骨架的病理学改变方面有明显的改善(P<0.05)。结果提示:罗格列酮可以改善3×Tg模型小鼠阿尔茨海默病(AD)样的学习记忆减退和Tau蛋白的过磷酸化表达。This study is to investigate the protective effect of rosiglitazone （RSG） against learning and memory impairment of APP/PS1/tau transgenic mice. AD mice model was replicated by using 6-month APP/PS1/tau transgenic mice. The learning and memory ability of mice was evaluated by Morris water maze and Western blotting assays was applied to measure the phosphorylation and O-glycosylation of Tau and neurofilaments （NFs） protein. The results demonstrated that RSG could reverse the learning and memory deficits of 3×Tg mice significantly. It was also found that RSG could suppress the hyperphosphorylation of Tau and NFs protein levels and increase the glycosylation expression of Tau and NFs proteins in 3 ×Tg mice brain. Together, RSG ameliorates cognitive impairments of 3×Tg mice via the alleviation of the hyperphosphorylated Tau and NFs proteins burden in the brain.

关 键 词：罗格列酮 阿尔茨海默病 TAU蛋白 神经丝 

分 类 号：R965[医药卫生—药理学]