盐诱导激酶1在有氧运动改善衰老小鼠神经炎性反应和学习记忆功能中的作用  

The role of salt induced kinase 1 in aerobic exercise improving neuroinflammatory response and learning and memory function in aged mice

作　　者：丁显怡 李雪[1] 周洪莲 金毓 魏昌玲 DING Xianyi;LI Xue;ZHOU Honglian(Chengdu Sport University,Chengdu,Sichuan,610041)

机构地区：[1]成都体育学院运动医学与健康学院,四川省成都市610041

出　　处：《中国康复医学杂志》2024年第11期1572-1580,1605,共10页Chinese Journal of Rehabilitation Medicine

基　　金：四川省运动医学重点实验室和国家体育总局重点实验室(2023-A025);成都体育学院“十四五”科学研究创新团队项目(23CXTD02)。

摘　　要：目的:探讨盐诱导激酶1(salt induced kinase 1,SIK1)在有氧运动对衰老小鼠神经炎性反应和空间学习记忆功能的影响中的作用。方法:雄性C57BL/6小鼠54只分为青年组(C组,n=18)、衰老组(A组,n=18)和衰老运动组(E组,n=18)。C组和A组小鼠自然喂养,E组小鼠进行8周有氧跑台运动干预。采用Morris水迷宫(morris water maze,MWM)实验评估小鼠的空间学习记忆功能,转录组测序(RNA sequencing,RNA-Seq)筛选运动改善衰老学习记忆功能的靶基因;免疫荧光实验检测离子钙结合适配器分子1(ionized calcium binding adaptor molecule 1,Iba-1)的荧光强度;实时PCR和Western Blot实验分别检测SIK1、核因子κB(nuclear factor kappa-B,NF-κB)、白介素1β(interleukin 1β,IL-1β)mRNA和蛋白表达水平。结果:衰老小鼠学习记忆功能相关指标平均逃避潜伏期增加,穿越平台次数减少(P<0.01);海马神经元显著破坏,小胶质细胞(microglia,MG)激活相关基因Iba-1荧光强度增加(P<0.01);小鼠海马转录组水平受到干扰,其中175个基因上调,66个基因下调;炎症相关基因SIK1、NF-κB m RNA(P<0.05,P<0.01)和蛋白(P<0.01,P<0.01)表达升高,IL-1β mRNA表达增加(P<0.05);运动干预后,衰老小鼠平均逃避潜伏期减少,穿越原平台次数增加(P<0.01),神经元损伤减弱,Iba-1荧光强度减弱(P<0.01),19个基因上调,12个基因下调,SIK1、NF-κB mRNA(P<0.01,P<0.05)和蛋白(P<0.05,P<0.05)表达降低,IL-1β蛋白表达降低(P<0.05)。结论:8周有氧运动可以降低衰老小鼠海马SIK1及其下游NF-κB、IL-1β的表达,抑制MG激活,减轻神经炎性反应,最终改善空间学习和记忆功能。Objective:To investigate the effects of salt induced kinase 1(SIK1)in the effects of aerobic exercise on neuroinflammatory response and spatial learning and memory function in aging mice.Method:Fifty-four male C57BL/6 mice were divided into three groups:the young group(group C,n=18),the aging control group(group A,n=18),and the aging exercise group(group E,n=18).Mice in groups C and A were fed naturally,while the mice in group E were subjected to aerobic treadmill exercise intervention for 8 weeks.Morris water maze training and testing were used to evaluate mice's spatial learning and memory abilities.Transcriptome sequencing was used to screen the differential genes.Immunofluorescence was used to detect the fluorescence intensity of ionized calcium-binding adaptor molecule 1(Iba-1).The mRNA and protein expression levels of SIK1,nuclear factor kappa-B(NF-κB)and interleukin 1β(IL-1β)were detected by real-time PCR and Western Blot.Result:The mean escape latency was prolonged and the number of crossings of the original platform was reduced(P<0.01)for learning and memory function-related indicators in aging mice;hippocampal neurons were significantly disrupted and microglia(MG)activation-related gene Iba-1 fluorescence intensity was increased(P<0.01);transcriptome levels were disturbed,with 175 genes upregulated and 66 genes were downregulated;inflammation-related genes SIK1,NF-κB mRNA(P<0.05,P<0.01)and protein(P<0.01,P<0.01)expression was elevated and IL-1βmRNA expression was increased(P<0.05).After exercise intervention,the mean escape latency was reduced and the number of crossing the original platform was increased in aging mice(P<0.01),attenuated neuronal damage,reduced Iba-1 fluorescence intensity(P<0.01),upregulation of 19 genes,downregulation of 12 genes,reduced expression of SIK1,NF-κB mRNA(P<0.01,P<0.05)and protein(P<0.05,P<0.05),and IL-1βprotein expression was reduced(P<0.05).Conclusion:Eight weeks of aerobic exercise can reduce the expression of hippocampal SIK1 and its downstream NF-κB and IL-1β

关 键 词：有氧运动 衰老 空间学习和记忆功能 神经炎性反应 SIK1 

分 类 号：R493[医药卫生—康复医学]