APP/PS1转基因AD模型小鼠海马自噬及相关信号通路研究Hippocampal autophagy and related signaling pathways in APP/PS1 transgenic Alzheimer's disease model mice
侯雪飞;龚仕涛;李锦超;李欣;
摘要(Abstract):
目的研究β-淀粉样前体蛋白/早老素1(amyloid precursor protein/presenilin 1,APP/PS1)双转基因阿尔茨海默病(Alzheimer disease,AD)模型小鼠不同年龄阶段自噬水平变化,及蛋白激酶B(protein kinase B,Akt)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)传统自噬信号通路的变化。方法选取4月龄、8月龄、12月龄APP/PS1转基因AD小鼠各4只,另选择同窝4月龄、8月龄、12月龄C57BL/6小鼠各4只为对照组。采用蛋白免疫印迹法检测各组小鼠海马自噬相关蛋白Akt、p-Akt、mTOR、p-mTOR、微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3,LC3)、选择性自噬接头蛋白(sequestosome-1,p62)的表达水平。结果与对照组比较,4月龄、8月龄APP/PS1转基因AD小鼠Akt、p-Akt、mTOR、p-mTOR、LC3、p62表达量均无统计学变化(均P>0.05),12月龄APP/PS1转基因AD小鼠p-Akt/Akt、p-Akt、LC3Ⅱ、LC3Ⅱ/LC3Ⅰ升高(P<0.05)。不同月龄APP/PS1小鼠海马LC3Ⅱ蛋白表达水平及LC3Ⅱ/LC3Ⅰ比较有统计学差异(P<0.05)。结论 APP/PS1转基因AD小鼠海马自噬与小鼠月龄有关。AD小鼠从12月龄开始出现自噬异常,Akt/mTOR信号通路异常激活。
关键词(KeyWords): 阿尔茨海默病;自噬;淀粉样β蛋白前体;早老素1;Akt激酶信号通路;哺乳动物雷帕霉素靶蛋白
基金项目(Foundation): 国家自然科学基金地区科学基金项目(31660273);; 云南省教育厅科学研究基金(2019Y0349);云南省教育厅科学研究基金指导性项目(2017zDX158)
作者(Author): 侯雪飞;龚仕涛;李锦超;李欣;
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