文章摘要
余鹏飞,吕梦倩,陈冬龙,王 宇,王 军,高 蓉,肖 杭.脑胰岛素信号在阿尔兹海默症模型小鼠渐进过程中的改变[J].南京医科大学学报,2019,(7):955~959
脑胰岛素信号在阿尔兹海默症模型小鼠渐进过程中的改变
Brain insulin signaling pathway and glucose homeostasis in APP/SP1 transgenic mice models of AD
投稿时间:2018-09-18  
DOI:10.7655/NYDXBNS20190702
中文关键词: AD模型鼠  胰岛素信号  阿尔兹海默症  淀粉样前体蛋白  Tau
英文关键词: transgenic mice models for AD  insulin pathway  Alzheimer’s disease(AD)  amyloid precusor protein(APP)  Tau
基金项目:国家自然科学基金(81673213,81202230);江苏省自然科学基金(BK20151557);江苏省高校自然科学基金(14KJB310009)
作者单位
余鹏飞 南京医科大学公共卫生学院江苏 南京 211166 
吕梦倩 南京医科大学公共卫生学院江苏 南京 211166 
陈冬龙 南京医科大学公共卫生学院江苏 南京 211166 
王 宇 南京医科大学公共卫生学院江苏 南京 211166 
王 军 南京医科大学公共卫生学院江苏 南京 211166 
高 蓉 南京医科大学公共卫生学院江苏 南京 211166 
肖 杭 南京医科大学公共卫生学院江苏 南京 211166 
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中文摘要:
      目的:探讨阿尔兹海默症(Alzheimer’s disease,AD)形成过程中脑胰岛素信号及葡萄糖转运体(glucose transporters,GLUTs)表达的改变,为AD早期诊断提供依据。方法:借助APP/PS1转基因AD模型小鼠,运用Western blot检测该模型鼠皮层和海马区域胰岛素信号通路相关蛋白的表达。结果:与对照组相比,AD模型鼠在3月龄时,表现为脑胰岛素信号应激性激活,下游AKT/GSK3β等胰岛素信号分子磷酸化水平升高,而GLUTs此时表达变化不明显;5月龄时,该模型表现为脑胰岛素信号磷酸化水平显著下降,其下游AKT/GSK3β等信号分子磷酸化水平表达下调,同时观察到海马中GLUT3、GLUT4表达下调,AD病理性蛋白(APP)、Tau蛋白磷酸化水平显著增加。结论:胰岛素信号紊乱和葡萄糖转运体在AD形成过程中发生紊乱,且随年龄增长,具有紊乱加剧的趋势。
英文摘要:
      Objective:This study was designed to explore the brain insulin signaling and the expression of glucose transporters(GLUTs)in APP/SP1 transgenic Alzheimer’s disease(AD)mice,it may provide the evidence for the early diagnosis of AD. Methods:Western blot was used to detect the expressions of insulin?signaling pathway related proteins in the cortex and hippocampus of the APP/PS1 transgenic AD model mice. Results:Our results showed that in the 3?month?old mice,brain insulin signaling was irritably activated,and the phosphorylation level of downstream AKT/GSK3β and other insulin signaling molecules increased,while the expression of GLUTs did not change significantly at this time. However,in the 5?month?old mice,it showed that the phosphorylation level of the brain insulin signal decreased significantly,and the phosphorylation level of its downstream AKT/GSK3β and other signaling molecules was down?regulated. At the same time,down?regulated expression of GLUT3 and GLUT4 was observed in the hippocampus,and the level of Tau protein phosphorylation(p?tau)was significantly increased. Conclusion:Our results confirmed that in APP/PS1 transgenic mice,brain insulin signaling pathway and glucose homeostasis were significantly disrupted in the process of AD formation,and the impairments increase with age.
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