摘要
背景:脊髓损伤引发神经-肌肉系统级联损伤涉及到中枢模式发生器功能失活及外周肌肉分子网络紊乱,运动能够调控特征基因并促进脊髓损伤康复。目的:利用生物信息学筛选靶向运动调控的特征基因,探索运动干预调节脊髓损伤恢复的发生机制。方法:通过GEO数据库下载基于GPL1355平台的GSE45550数据集,筛选大鼠脊髓损伤亚急性期急性运动与短期运动干预所调控的相关差异基因,并对相关差异基因进行GO功能富集分析、KEGG信号通路、GSEA富集分析,以及建立蛋白互作网络。结果与结论:①大鼠脊髓损伤亚急性期进行急性运动干预后腓肠肌106个基因上调,97个基因下调;短期运动干预后138个基因上调,105个基因下调;②GO分析表明,急性运动干预后差异基因主要富集于染色体分离;短期运动干预主要促进了信号转导等过程;KEGG分析表明急性运动干预主要与胃酸分泌、运动蛋白通路上调等有关;短期运动干预主要涉及神经活性配体受体互作上调及部分炎症信号通路下调;③GSEA分析显示,急性运动干预主要上调细胞周期、DNA分离;短期运动干预主要下调白细胞介素17信号、肿瘤坏死因子信号通路;④蛋白互作网络显示,急性运动干预与短期运动干预分别形成2,3个中心作用模块。总而言之,急性运动干预显著激活细胞增殖相关通路(如细胞周期、有丝分裂),上调Top2a、Sele等促增殖基因表达;而短期干预则通过下调白细胞介素17、肿瘤坏死因子等炎症通路,下调COMP等因子表达发挥抗炎作用,这些发现为脊髓损伤康复的分子机制研究提供了参考依据。
BACKGROUND:Spinal cord injury triggers a cascade of neuro-muscular system damage,involving central pattern generator dysfunction and peripheral muscle molecular network disruptions.Exercise can regulate key genes and promote the recovery of spinal cord injury.OBJECTIVE:To identify exercise-regulated key genes through bioinformatics analysis and explore the mechanisms by which exercise intervention facilitates the recovery of spinal cord injury.METHODS:The GSE45550 dataset based on the GPL1355 platform was obtained from the Gene Expression Omnibus(GEO)database.Differentially expressed genes regulated by acute and short-term exercise interventions during the subacute phase of spinal cord injury in rats were identified.Gene Ontology functional enrichment analysis,Kyoto Encyclopedia of Genes and Genomes pathway analysis,and Gene Set Enrichment Analysis were performed on these differentially expressed genes,and a protein-protein interaction network was constructed.RESULTS AND CONCLUSION:(1)After acute exercise intervention in the subacute phase of spinal cord injury,106 genes were upregulated and 97 genes were downregulated in the gastrocnemius muscle,whereas short-term exercise intervention resulted in 138 upregulated and 105 downregulated genes.(2)Gene Ontology analysis showed that acute exercise mainly enriched genes related to chromosome segregation,while short-term exercise primarily promoted signal transduction processes.Kyoto Encyclopedia of Genes and Genomes analysis revealed that acute exercise was associated with the upregulation of pathways related to gastric acid secretion and motor protein function,whereas short-term exercise upregulated neuroactive ligand-receptor interactions and downregulated inflammatory pathways.(3)Gene Set Enrichment Analysis indicated that acute exercise intervention mainly upregulated cell cycle and DNA segregation pathways,while short-term intervention led to downregulation of the interleukin-17 and tumor necrosis factor signaling pathways.(4)The proteinprotein interaction network revealed two key functional modules in acute exercise intervention and three in short-term intervention.In summary,acute exercise significantly activated cell proliferation-related pathways(e.g.,cell cycle and mitosis)and upregulated pro-proliferative genes such as Top2a and Sele.In contrast,short-term intervention exerted anti-inflammatory effects by downregulating interleukin-17 and tumor necrosis factor signaling pathways and reducing the expression of inflammatory factors such as COMP.These findings provide insights into molecular mechanisms of spinal cord injury recovery.
作者
魏心怡
郑艳
陈前
任佳佳
李健
Wei Xinyi;Zheng Yan;Chen Qian;Ren Jiajia;Li Jian(School of Physical Education and Health,East China Normal University,Shanghai 200241,China;School of Physical Education,Soochow University,Suzhou 215021,Jiangsu Province,China;School of Physical Education,Xi’an Shiyou University,Xi’an 710065,Shaanxi Province,China;Peking University Health Science Center,Beijing 100191,China)
出处
《中国组织工程研究》
北大核心
2026年第24期6196-6206,共11页
Chinese Journal of Tissue Engineering Research
关键词
脊髓损伤
运动干预
分子机制
生物信息学
时序性
康复
细胞周期
炎症通路
spinal cord injury
exercise intervention
molecular mechanism
bioinformatics
temporality
rehabilitation
cell cycle
inflammatory pathway
