罗格列酮对三重转基因小鼠认知障碍的干预作用

发布时间：2018-06-16 04:38

本文选题：罗格列酮 + 阿尔茨海默病　；参考：《药学学报》2014年06期

【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(P0.05);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(P0.05);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(P0.05)。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。
[Abstract]:To observe the effect of insulin sensitizer rosiglitazone on cognitive impairment in 3 脳 TG mice. Male C57 / BL6 mice were divided into normal control group (WT group) and drug intervention group (RSG group). Male APP / PS1 / tau transgenic mice were randomly divided into model group (3 脳 TG model group) and rosiglitazone treatment group (3 脳 TG RSG group). And rosiglitazone 2.5 mg kg-1 d -1 for 8 weeks. The other groups were given the same amount of normal saline, Morris water maze test was used to evaluate the cognitive function of mice, and the phosphorylation and glycosylation levels of Tau protein and NFS protein were detected by Western blot. The results showed that compared with WT group and RSG group, the escape latency and path length in the 3 脳 TG model group were significantly increased, and the residence time in the quadrant and the number of times of passing through the hidden platform were significantly decreased (P 0.05). The phosphorylation of Tau protein and NFS protein in the brain of the model mice was significantly increased, while the expression of glycosylated associated protein was significantly decreased in the model mice, but in the 3 脳 TG RSG treatment group, the above behavioral and cytoskeletal pathological changes were significantly improved. The results suggested that rosiglitazone could improve AD-like learning and memory impairment and the overexpression of Tau protein in 3 脳 TG mice.
【作者单位】：天津医科大学基础医学院;
【基金】：国家自然科学基金资助项目(30973156,81270422)
【分类号】：R749.16

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