有氧运动对APP/PS1小鼠海马内质网应激-细胞自噬偶联的影响  

Effects of Aerobic Exercise on Endoplasmic Reticulum Stress and Autophagy Coupling in Hippocampus of APP/PS1 Mice

作　　者：夏杰[1,2] 赵娜[1,2] 王璟[1,2] 李百侠[1,2] 徐波 XIA Jie;ZHAO Na;WANG Jing;LI Baixia;XU Bo(College of Physical Education and Health,East China Normal University,Shanghai 200241,China;Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education,East China Normal University,Shanghai 200241,China)

机构地区：[1]华东师范大学体育与健康学院,上海200241 [2]华东师范大学“青少年健康评价与运动干预”教育部重点实验室,上海200241

出　　处：《体育科学》2022年第8期55-65,共11页China Sport Science

基　　金：国家自然科学基金项目(31571225)。

摘　　要：目的:探究3个月的中等强度有氧运动对APP/PS1小鼠海马Aβ病理及内质网应激-细胞自噬偶联的影响。方法:将3月龄雄性野生型小鼠和APP/PS1转基因小鼠分为野生型对照组(WT-Sed)、野生型运动组(WT-Exe)、APP/PS1对照组(APP/PS1-Sed)和APP/PS1运动组(APP/PS1-Exe)。APP/PS1-Exe组和WT-Exe组小鼠进行为期3个月的有氧跑台运动干预。运动干预结束后,采用免疫组织化学检测海马Aβ斑块、APP与GRP78共标、CRT与LC3共标;Simple Western、Western blotting检测海马PERK、p-PERK、eIF2α、p-eIF2α、ATF4、LC3、P62和CRT的蛋白表达水平;Real-time PCR检测海马BECN1、ATG5、ATG7和ATG12的mRNA水平。结果:与WT-Sed组相比,APP/PS1-Sed组小鼠海马Aβ斑块水平、APP/GRP78共定位水平以及APP和GRP78的平均荧光强度显著增加;p-PERK、p-eIF2α和ATF4的蛋白水平显著升高;BECN1和ATG7的mRNA水平显著降低,ATG12的mRNA水平、LC3Ⅱ和P62的蛋白水平显著升高;CRT的mRNA、蛋白水平以及平均荧光强度显著降低,LC3的平均荧光强度显著增加。与APP/PS1-Sed组相比,APP/PS1-Exe组小鼠海马Aβ斑块水平、APP/GRP78共定位水平、GRP78的平均荧光强度显著降低;p-PERK、p-eIF2α、ATF4的蛋白水平显著降低;ATG12的mRNA水平显著升高,P62的蛋白水平显著降低;CRT的蛋白水平和平均荧光强度显著增加。结论:跑台运动可以减少APP在小鼠内质网中积累,缓解内质网应激并抑制PERK/eIF2α过度激活,进而提高自噬活性并上调CRT介导的内质网应激-细胞自噬偶联,从而有益于减少AD脑内错误折叠蛋白质的生成和聚集。Objective:To explore the effects of 3 months moderate intensity aerobic exercise on AD pathology and endoplasmic reticulum stress autophagy coupling in APP/PS1 mice.Methods:3-month old male APP/PS1 transgenic mice and wild type mice were randomly divided into wild type control group(WT-Sed),wild type exercise group(WT-Exe),APP/PS1 control group(APP/PS1-Sed)and APP/PS1 exercise group(APP/PS1-Exe).Mice in APP/PS1-Exe group and WT-Exe group were subjected to treadmill exercise for 3 months.After intervention,the immunohistochemistry was used to detect the Aβplaque,the co-localization of APP and GRP78,CRT and LC3 in hippocampus.Western blotting and Simple western were used to detect the protein levels of PERK,p-PERK,eIF2α,p-eIF2α,ATF4,LC3,P62 and CRT in hippocampus.Real-time PCR was used to detect the mRNA levels of ATG5,ATG7,ATG12,BECN1 and CRT in hippocampus.Results:Compared with WT-Sed group,the level of Aβplaque,the colocalization level of APP/GRP78 and the average fluorescence intensity of APP and GRP78 were significantly increased in APP/PS1-Sed mice;the protein levels of p-PERK,p-eIF2αand ATF4 were significantly increased in APP/PS1-Sed mice;the mRNA levels of BECN1 and ATG7 were significantly decreased,the mRNA level of ATG12 and the protein levels of LC3Ⅱand P62 were significantly increased,the mRNA and protein levels of CRT were significantly decreased in APP/PS1-Sed mice;the average fluorescence intensity of CRT was significantly decreased,and the average fluorescence intensity of LC3 was significantly increased in APP/PS1-Sed mice.Compared with APP/PS1-Sed group,the level of Aβplaque,the co-localization level of APP/GRP78 and the average fluorescence intensity of GRP78 in APP/PS1-Exe mice were significantly decreased;the protein levels of p-PERK,p-eIF2αand ATF4 in APP/PS1-Exe mice were significantly decreased;the mRNA level of ATG12 was significantly increased,and the protein level of P62 was significantly decreased in APP/PS1-Exe mice;the protein level of CRT,and the average fluorescence intensi

关 键 词：阿尔茨海默病 跑台运动 内质网应激 细胞自噬 钙网蛋白 

分 类 号：G804.2[文化科学—运动人体科学]