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

作　　者：侯雪飞 龚仕涛 李锦超 李欣 HOU Xuefei;GONG Shitao;LI Jinchao;LI Xin(不详;Yunnan Key Laboratory of Stem Cell and Regenerative Medicine,Biomedical Engineering Research Center,Kunming Medical University,Kunming Yunnan 650500,China)

机构地区：[1]昆明医科大学生物医学工程研究中心,云南省干细胞和再生医学重点实验室,650500

出　　处：《中国神经免疫学和神经病学杂志》2021年第1期53-57,共5页Chinese Journal of Neuroimmunology and Neurology

基　　金：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)。

摘　　要：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。Objective To investigate the changes of autophagy level and Akt/mTOR signaling pathway in APP/PS1 dual-transgenic Alzheimer's disease(AD)mice at different age stages.Methods 4 APP/PS1 transgenic AD mice aged 4 months,8 months and 12 months were selected,and 4 C57BL/6 mice aged 4 months,8 months and 12 months were selected as control groups.The expression levels of autophagy associated proteins Akt,p-Akt,mTOR,p-MTOR,microtubule associated protein 1 light chain 3(LC3)and selective autophagy adaptor protein(sequestosome-1,p62)in the hippocampus of mice in each group were detected by protein western blot.Results Compared with the control groups,4 and 8 months APP/PS1 transgenic mice had no change in Akt,p-Akt,mTOR,p-mTOR,LC3,p62 expression levels(P>0.05),but twelve months APP/PS1 transgenic mice had significantly increased Akt/Akt,p-Akt,LC3Ⅱ,LC3Ⅱ/LC3Ⅰexpression levels(P<0.05).APP/PS1 mice of different months had significant differences in hippocampus LC3Ⅱprotein expression levels and LC3Ⅱ/LC3Ⅰ(P<0.05).Conclusions The hippocampal autophagy of APP/PS1 transgenic mice was related to the age of mice.AD mice showed abnormal autophagy and abnormal activation of Akt/mTOR signaling pathway at the age of 12 months.

关 键 词：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 

分 类 号：R742.8[医药卫生—神经病学与精神病学]