有氧运动对青年期小鼠海马体Cdc42及DNA损伤反应相关因子的短期和长期影响  

Short-term and long-term effects of aerobic exercise on the expression of hippocampi Cdc42 and DNA-damage response in adolescent mice

作　　者：骆远 宋诗语 赵格 彭爽 李良鸣[1] 刘淑靖 LUO Yuan;SONG Shiyu;ZHAO Ge;PENG Shuang;LI Liangming;LIU Shu-jing(Guangzhou Sport University,Guangzhou 510500,China;Guangzhou Institute of Science and Technology,Guangzhou 510540,China;Guangdong University of Science and Technology,Dongguan 523083,China)

机构地区：[1]广州体育学院,广东广州510500 [2]广州理工学院,广东广州510540 [3]广东科技学院,广东东莞523083

出　　处：《中国病理生理杂志》2023年第11期1956-1963,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.32100920);广东省自然科学基金面上项目(No.2023A1515012678)。

摘　　要：目的:探讨有氧运动对青年期小鼠海马体细胞分裂周期蛋白42(cell division cycle protein 42,Cdc42)及DNA损伤反应(DNA-damage response,DDR)相关因子的短期和长期影响。方法:构建运动小鼠模型,将40只8周龄SPF级C57BL/6雄性小鼠随机分为安静组和运动组,每组20只,均使用普通饲料喂养。运动组小鼠进行12周的中等强度(75%VO_(2)max)跑台运动,安静组小鼠在不跑步的情况下暴露于跑步机噪声和振动中。12周训练结束后,从安静组和运动组中随机选取小鼠各10只(5月龄),分别为安静青年期小鼠(Sed-young)组和运动青年期小鼠(Exe-young)组;剩余的10只安静组小鼠和10只运动组小鼠继续喂养至老年期(18月龄),作为安静老年期小鼠(Sed-old)组和运动老年期小鼠(Exe-old)组。所有小鼠均收集Y迷宫、体成分数据及海马体组织,通过Cdc42活性检测和Western blot法比较各组小鼠海马体Cdc42-GTP活性及Cdc42蛋白表达情况,通过RT-qPCR比较各组小鼠海马体Cdc42、Pak4、Pak5、Cofilin、Chk2、Atm和P53等DDR相关因子的mRNA水平。结果:与安静组比较,有氧运动可显著降低青年期小鼠脂肪百分比(P<0.05),显著提高空间识别记忆能力(P<0.05),并维持至老年期(P<0.05)。与安静组比较,运动青年期小鼠和运动老年期小鼠海马体Cdc42表达及活性均显著降低(P<0.05)。与安静组比较,有氧运动显著降低青年期小鼠海马体Cdc42、Pak4、Pak5、Cofilin、Atm、Chk2和P53的转录水平(P<0.05);其中,Cdc42、Pak4、Pak5、Cofilin、Chk2和P53的转录水平下降可维持至老年期(P<0.05)。结论:青年期进行的有氧运动可持续抑制小鼠海马体Cdc42及DDR相关因子的表达,保护海马体神经元细胞免受DNA损伤而死亡或衰老直至老年期。AIM:This study aims to examine the short-term and long-term effects of aerobic exercise on the cell division cycle protein 42(Cdc42)and DNA-damage response(DDR)-related factors in the hippocampus of adolescent mice.METHODS:A cohort of 40 C57BL/6 male mice,aged 8 weeks,was randomly divided into two groups:a sedentary group and an exercise group,each consisting of twenty mice,respectively.Both groups were provided with a standard diet.The exercise group underwent a 12-week treadmill exercise regimen at a moderate intensity level of 75%VO_(2)max.The sedentary group,serving as the control,was exposed to treadmill noise and vibration without engaging in any physical activity.Ten mice from the sedentary group and 10 mice from the exercise group,all aged 5 months,were randomly as‑signed to the sedentary young(Sed-young)group and the exercise young(Exe-young)group.The remaining 10 mice from each group were designated as the sedentary old(Sed-old)group and the exercise old(Exe-old)group.These mice were allowed to continue their respective diets fed until they reached 18 months of age.At the end of the study,all mice under-went Y-maze testing,body composition analysis,and had their hippocampal tissue collected for further analysis.The pro-tein expression and activity of hippocampal Cdc42 were detected by Western blot and pull-down assays.The relative ex-pression levels of hippocampal Cdc42,Pak4,Pak5,Cofilin,Chk2,Atm and P53 in the mice were determined using RT-qPCR.RESULTS:Adolescent mice that engaged in aerobic exercise exhibited reduced body fat percentages(P<0.05)and demonstrated enhanced spatial awareness and memory abilities(P<0.05)that could persisted throughout their lifes-pan(P<0.05).In both young and old age,the exercise group displayed significantly diminished expression and activity of the Cdc42 protein in the hippocampus compared to the sedentary group.Furthermore,the hippocampus of adolescent mice exhibited significantly decreased transcriptional levels of Cdc42,Pak4,Pak5,Cofilin,Atm,Chk2 and P53 following a

关 键 词：运动 海马体 细胞分裂周期蛋白42 DNA损伤反应 衰老 

分 类 号：R87[医药卫生—运动医学] R363.2[医药卫生—临床医学] R339.4