抗阻运动经JAK2/STAT5a改善SAMP8小鼠肌少症的作用机制  

Mechanism of resistance exercise in improving sarcopenia in SAMP8 mice through the JAK2/STAT5apathway

作　　者：曲波 李伦宇 黄盈 邓长青 丁海丽[1,2] QU Bo;LI Lunyu;HUANG Ying(School of Sports Medicine and Health,Chengdu Sport University,Chengdu,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 [2]成都体育学院运动医学与健康研究所

出　　处：《中国康复医学杂志》2024年第12期1756-1765,共10页Chinese Journal of Rehabilitation Medicine

基　　金：国家自然科学基金资助项目(81904318);四川省中央引导地方科技发展项目(2022ZYD0062);四川省自然科学基金(2023NSFSC0545);四川省科技创新创业苗子工程(2023JDRC0100)。

摘　　要：目的:基于转录组学探讨抗阻运动经JAK2/STAT5a通路改善肌少症的作用机制。方法:将16只28周龄雄性SAMP8小鼠随机分为模型老化组(M组)、抗阻训练组(R组);另设8只同龄雄性抗衰老小鼠(SAMR1)作为C组(年轻对照组)。C组、M组常规饲养,不进行任何干预,R组进行8周递增式负重爬梯训练。每周测定相对抓力和转棒时间,干预结束后测试小鼠肌肉相对质量、观察肌纤维横截面积;利用RNA-seq技术建库转录组测序,筛选差异表达基因,通过GO、KEGG富集显著性差异表达基因的相关生理特性和高相关信号通路,PPI筛选相关核心基因;RT-qPCR检测骨骼肌IL-6、Jak2、Stat5a及Socs3的mRNA的表达。结果:①小鼠相对抓力、转棒时长及肌肉质量结果显示,M组显著低于C组(P<0.001);R组则显著高于M组(P<0.05);HE染色观察肌肉横截面积结果显示,M组显著低于C组(P<0.001);而R组显著高于M组(P<0.05);转录组差异基因筛选:R组和M组共筛选出572个DEGs,相较于M组,R组231个mRNA表达上调,341个mRNA表达下调(FC≥0,P<0.05);通过DEGs GO、KEGG分析富集分析发现JAK-STAT信号通路高表达;PPI筛选出肌少症核心基因JAK2、STAT5a。RT-qPCR结果显示,相较于C组,M组骨骼肌IL-6、Jak2、STAT5a的基因表达水平显著增加(P<0.01),Socs3表达水平显著降低(P<0.01);相较于M组,R组骨骼肌IL-6 mRNA、JAK2及STAT5a含量显著下降(P<0.05),Socs3含量则显著升高(P<0.01)。结论:抗阻运动能够通过抑制JAK2/STAT5a通路改善SAMP8小鼠肌少症。Objective:To explore the mechanism of resistance exercise improving sarcopenia through JAK2/STAT5a pathway based on transcriptomics.Method:Sixteen 28-week-old male SAMP8 mice were randomly divided into an aging model group(GroupM)and a resistance training group(Group R);another eight age-matched male anti-aging mice(SAMR1)were set up as Group C(the young control group).Groups C and Group M were routinely housed withoutany interventions,and Group R underwent 8 weeks of incremental load ladder climbing training.The relativegrip strength and rotating rod time were measured every two weeks,and at the end of the intervention,therelative muscle mass of the mice was tested and the cross-sectional area of muscle fibers was observed;RNAseq technology was used to build libraries for transcriptome sequencing,to screen for differentially expressed genes,and to enrich relevant physiological characteristics and highly relevant signaling pathways through GO,KEGG enrichment,with PPI screening for related core genes;RT-qPCR was used to detect mRNA expressionof IL-6,Jak2,Stat5a and Socs3 in skeletal muscle.Result:①Relative grip strength,rotating rod time and muscle mass of the mice showed that group M wassignificantly lower than group C(P<0.001),while group R was significantly higher than group M(P<0.05);The HE staining of muscle cross-sectional area showed group M was significantly lower than group C(P<0.001),while group R was significantly higher than group M(P<0.05);Transcriptomic differential genescreening:a total of 572 DEGs were screened between groups R and M,with 231 mRNA expressions upregulated and 341 mRNA expressions downregulated in group R compared to group M(FC≥0,P<0.05);JAKSTAT signaling pathway was found to be highly expressed by enrichment analysis of DEGs GO and KEGG;PPI screened for the core genes of sarcopenia core genes JAK2,STAT5a.RT-qPCR results showed that compared to group C,the gene expression levels of IL-6,Jak2,and STAT5a in skeletal muscle in group M weresignificantly increased(P<0.01),and the expr

关 键 词：抗阻运动 肌少症 JAK/STATa 转录组 IL-6 SAMP8小鼠 

分 类 号：R493[医药卫生—康复医学] R684.3[医药卫生—临床医学]