首页|抗阻运动对SAMP8小鼠骨骼肌lncRNA和mRNA基因表达谱的影响

抗阻运动对SAMP8小鼠骨骼肌lncRNA和mRNA基因表达谱的影响

Effects of resistance exercise on long non-coding RNA and mRNA expression profiles of skeletal muscle in senescence accelerated-prone 8 mice

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
目的 利用RNA-seq技术比较运动组与对照组小鼠股四头肌中差异表达的lncRNA和mRNA,探讨抗阻运动作用于SAMP8 小鼠的潜在调控机制.方法 12 只 28 周龄雄性SAMP8 快速衰老小鼠分为模型组(M组)、抗阻运动组(R组),每组 6 只;另设 6 只同龄SAMR1 抗衰老小鼠作对照组(C组).R组经递增负重爬梯运动训练 8 周.每 1 周测定相对抓力、每 2 周测转棒测试时间.取材后取右侧股四头肌进行苏木素-伊红(HE)染色观察其组织学变化;并取左侧股四头肌进行RNA-seq,筛选出差异表达的lncRNA(long non-coding RNA,lncRNA)和mRNA,然后对这些基因进行基因本体(Gene Ontology,GO)、京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析.结果 (1)干预前,SAMP8 小鼠相比较于自然衰老的SAMR1 小鼠表现出相对抓力以及加速转棒测试时长显著下降(P＜0.01);干预后,与M组相比,R组相对抓力以及转棒时长均出现显著增加(P＜0.01).(2)HE染色结果显示,M组肌纤维横截面积与C组比较显著下降(P＜0.01);R组肌纤维横截面积与 M组比较显著增加(P＜0.01).(3)通过差异表达分析,相比于M组,R组有 182 个表达水平上调和 218个表达下调的lncRNA以及 454 个表达上调和 289 个表达下调的mRNA.R组与M组之间差异lncRNA的靶基因KEGG显著富集的通路有产生IgA的肠道免疫网络、NF-κB、炎症性肠病等信号通路.结论 (1)本研究证明了抗阻运动能够改善SAMP8 小鼠肌少症的骨骼肌机能,利用RNA-seq分别鉴定出M组、R组小鼠的差异 lncRNA和mRNA.这些差异基因可能是肌少症的潜在治疗靶点.(2)通过分析差异表达lncRNA的靶基因以及mRNA的生物学信息,从而为进一步了解抗阻运动改善肌少症的机制提供了可能.
Objective To explore the potential regulatory mechanism of resistance exercise in senescence accelerated-prone 8 mice(SAMP8)by evaluating the effects of exercise on the expression of long non-coding RNA(lncRNA)and mRNA in quadriceps muscles by RNA-sequencing(RNA-seq)technology.Methods Twenty-eight-week-old male SAMP8 mice were divided into a model group(M group)and resistance-exercise group(R group)(n=6 mice per group).Another eight normally aging SAMR1 mice of the same age were used as the control group(C group).Mice in R group received 8 weeks of increasing weight climbing exercise training.Relative grip strength was measured every week and the rotarod test was performed every 2 weeks.Histological changes in the right quadriceps femoris were observed by hematoxylin-eosin staining and the left quadriceps was used for RNA-seq.Differentially expressed lncRNA and mRNA were screened and analyzed for enrichment by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses.Finally,key differentially expressed genes were analyzed by quantitative reverse transcription-polymerase chain reaction to verify the accuracy of the RNA-seq result.Results(1)Relative grip strength and rotarod test time were significantly decreased in M group compared with C group(P＜0.01),but were significantly increased after 8 weeks of Rgroup compared with M group(P＜0.01).(2)The cross-sectional area of the muscle fibers was significantly lower in M group compared with C group,as shown by HE staining(P＜0.01),while the cross-sectional area of the muscle fibers was significantly increased in the R group compared with M group(P＜0.01).(3)Differential expression analysis identified 182 upregulated and 218 downregulated lncRNA,and 454 upregulated and 289 downregulated mRNA between M group and R group.The KEGG pathways of lncRNA target genes that were differentially expressed between M group and R group were significantly enriched in intestinal immune network for IgA production,nuclear factor-kappa B signaling pathway,and inflammatory bowel disease.Conclusions(1)This study demonstrated that resistance exercise can improve skeletal muscle function in SAMP8 mice with sarcopenia.We identified lncRNA and mRNA that were differentially expressed as a result of resistance exercise,and which might be potential targets of sarcopenia therapy.(2)Furthermore,analyzing the biological functions of the target genes of the differentially expressed lncRNA and mRNA may further our understanding of the mechanism of resistance exercise for improving sarcopenia.

long non-coding RNASAMP8sarcopeniatranscriptomeresistance exercise

傅泽铤、李仲豪、李伦宇、刘洪政、丁海丽

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成都体育学院运动医学与健康研究所,成都 610041

贵阳市白云区第三中学,贵阳 550014

长非编码RNA SAMP8 肌少症 转录组 抗阻运动

国家自然科学基金四川省自然科学基金四川省中央引导地方科技发展专项国家体育总局运动医学重点实验室项目运动医学四川省重点实验室项目四川省科技创新创业苗子工程项目

819043182023NSFSC05452022ZYD00622018YFF03009042021-A0302023JDRC0100

2024

10.3969/j.issn.1005-4847.2024.03.002

中国实验动物学报
中国实验动物学会，中国医学科学院医学实验动物研究所

中国实验动物学报

CSTPCD北大核心
影响因子：0.767
ISSN：1005-4847
年,卷(期)：2024.32(3)
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