有氧运动对不同年龄小鼠海马mTOR信号通路活性的影响及其与认知功能关系  

Effects of aerobic exercise on mTOR signaling pathway in hippocampus of mice with different ages and its relationship with cognitive function

作　　者：杨风英 隋波[1] 杨杰[1] 傅力[2] Yang Fengying;Sui Bo;Yang Jie;Fu Li(College of Sport and Health,Shandong Sport University,Jinan 250102,China;School of Medical Technology,Tianjin Medical University,Tianjin 300070,China)

机构地区：[1]山东体育学院运动与健康学院,济南250102 [2]天津医科大学医学技术学院,天津300070

出　　处：《中国运动医学杂志》2025年第1期44-52,共9页Chinese Journal of Sports Medicine

基　　金：山东省自然科学基金面上项目(ZR2022MH163);国家自然科学青年基金(81601962)。

摘　　要：目的:探讨有氧运动对不同年龄小鼠海马哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路活性的影响及其与认知功能的关系。方法:将1月龄C57BL/6雄性小鼠90只,随机分为有氧运动(E)组(n=45)和安静对照(C)组(n=45),有氧运动组小鼠进行75%VO2max强度的有氧跑台运动干预;两组分别至小鼠3、12、20月龄时,行Morris水迷宫实验测试认知功能后,处死取材(n=15);采用Western blot法检测小鼠海马mTOR信号通路蛋白mTOR、mTOR丝氨酸2448位点磷酸化[p-mTOR(Ser2448)]、核糖体S6蛋白激酶1苏氨酸389位点磷酸化[p-S6K1(Thr389)]、真核生物翻译起始因子4E结合蛋白丝氨酸65位点磷酸化[p-4EBP1(Ser65)]及其上游脑源性神经营养因子(brainderived neurotrophic factor,BDNF)表达水平;采用免疫组织化学染色法检测小鼠海马BDNF蛋白阳性细胞并计算积分光密度。结果:水迷宫定位航行试验第3天开始,12月龄和20月龄小鼠逃避潜伏期显著长于3月龄小鼠(P<0.05,P<0.01),且20月龄较12月龄逃避潜伏期更长(P<0.05,P<0.01);目标象限航程和原平台位置穿越次数,12月龄小鼠显著低于3月龄小鼠(P<0.05),20月龄小鼠目标象限航程显著低于3、12月龄小鼠(P<0.01)。与同龄对照组相比,运动组逃避潜伏期显著缩短(P<0.05),目标象限航程显著增加(P<0.01)。20月龄小鼠p-mTOR(Ser2448)、p-S6K1(Thr389)、p-4EBP1(Ser65)及BDNF表达水平显著低于3月龄或12月龄小鼠(P<0.05,P<0.01);对于3月龄小鼠海马p-mTOR(Ser2448)、p-S6K1(Thr389)、p-4EBP1(Ser65)表达水平,运动组显著高于对照组(P<0.01);对于12和20月龄小鼠p-mTOR(Ser2448)、p-S6K1(Thr389)、p-4EBP1(Ser65)表达水平,运动组显著低于同龄对照组(P<0.05,P<0.01);与同龄对照组相比,运动组小鼠海马BDNF的表达水平显著提高(P<0.01)。结论:有氧运动促进幼年小鼠认知功能发育并延缓老年小鼠认知功能增龄性退变,这一作用效果可能通过激活幼年小鼠海马mTOObjective To explore the effect of aerobic exercise on the activity of mammalian target of rapamycin(mTOR)signaling pathway in hippocampus of mice with different ages and its relationship with cognitive function.Methods Ninety one-month-old C57BL/6 male mice were randomly divided into an aerobic exercise group(E,n=45)and a quiet control group(C,n=45).Group E was subjected to aerobic treadmill exercise with 75%VO2maxintensity,while group C kept quiet.When they grew to 3,12 and 20 months,15 of them underwent Morris water maze test to test the cognitive function before they were executed for their brain and hippocampus.Then,Western blotting was employed to detect the expression of mTOR,p-mTOR(Ser2448),p-S6K1(Thr389),p-4EBP1(Ser65)and brainderived neurotrophic factor(BDNF),while immunohistochemical staining was used to detect BDNF protein positive cells in the hippocampus and the integrated optical density was calculated.Results From day 3,the escape latencies in water maze navigation test of 12-month and 20-month mice were significantly higher than the 3-month ones(P<0.05 or P<0.01),with those of the 20-month significantly higher than the 12-month(P<0.05 or P<0.01).Moreover,the distance in target quadrant and number of platform location crossing of the 12-month were significantly lower compared with the 3-month(P<0.05),while those of the 20-month mice were significantly lower than the 3-and 12-month(P<0.01).For 3-month old mice,p-mTOR(Ser2448),p-S6K1(Thr389),and p-4EBP1(Ser65)expressions in group E were significantly higher than group C(P<0.05 or P<0.01);but for the 12-and 20-monthold mice,p-mTOR(Ser2448),p-S6K1(Thr389),and p-4EBP1(Ser65)expressions in group E were significantly lower than those of the age-matched C groups(P<0.05 or P<0.01).Meanwhile,the expression of BDNF in hippocampus of group E was significantly higher than the age-matched C groups(P<0.01).Conclusion Aerobic exercise can promote the development of cognitive function in young mice and delay the age-related degeneration in older mice,which may be

关 键 词：有氧运动 脑源性神经营养因子 哺乳动物雷帕霉素靶蛋白 海马 认知 

分 类 号：G804.2[文化科学—运动人体科学] R741[文化科学—体育学]