阿尔茨海默病小鼠肌肉组织中基因表达差异相关通路分析

Correlation analysis of differential gene expression pathways in muscle tissue of Alzheimer's disease mice

目的探讨阿尔茨海默病小鼠肌肉组织和正常小鼠肌肉组织转录组差异表达基因,阐述差异表达基因在阿尔茨海默病发病机制中的作用。方法收集阿尔茨海默病小鼠(10只)和健康小鼠(10只)肌肉组织,运用二代高通量RNA转录测序(RNA-seq)技术进行测序,筛选差异表达基因,并对其进行基因功能注释(GO)及京都基因与基因组百科全书(KEGG)通路分析。实时荧光定量聚合酶链反应(qRT-PCR)验证候选基因在阿尔茨海默病和正常小鼠肌肉组织中的表达差异。结果 4 222个基因在阿尔茨海默病小鼠和健康小鼠肌肉中表达差异有统计学意义(P<0.05或P<0.01),其中2 087个在阿尔茨海默病小鼠肌肉中高表达,2 135个低表达。GO分析结果显示,显著上调的功能基因主要富集于细胞过程、单一生物过程、代谢过程和催化活性等;KEGG通路分析结果表明,差异基因明显富集于代谢和炎症相关的信号通路等;qRT-PCR结果显示,候选基因表达趋势与转录组测序结果一致。结论在转录组水平上筛选出阿尔茨海默病小鼠和健康小鼠肌肉组织差异表达基因及相关重要调节信号通路,阿尔茨海默病小鼠肌肉组织中代谢和炎症相关通路最为富集,为深入探讨阿尔茨海默病发病机制提供重要的基础。

Objective To investigate differentially expressed genes in muscular tissue in Alzheimer’s disease mice and normal mice,and to elucidate the role of differentially expressed genes in the pathogenesis of Alzheimefs disease.Methods Muscle tissues of Alzheimer^s disease mice and normal mice were collected and the second-generation high-throughput RNA transcription sequencingC RNA-seq)technique was used to screen differentially expressed genes.Additionally,Gene Ontology(GO)functional annotation and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis were conducted.Differences in the expression of candidate genes in muscle tissues between Alzheimer,s mice and normal mice were verified by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Results A total of 4222 genes in muscles had different expression between Alzheimefs disease mice and normal mice,with 2087 genes highly expressed and 2135 lowly expressed in muscles of Alzheimer’s disease mice.GO analysis showed that significantly up-regulated functional genes were mainly enriched in cellular,single biological.metabolic and catalytic processes and activities.KEGG pathway analysis showed that differentially expressed genes were significantly enriched in signal pathways related to metabolism and inflammation.Results from qRT-PCR showed that the mRNA expression of candidate genes was consistent with the trend of transcriptome sequencing results.Conclusions Differentially expressed genes and related important regulatory signal pathways were screened at the transcriptome level in muscle tissues of Alzheimer's disease mice and normal mice.The differentially expressed genes are enriched in signal pathways related to metabolism and inflammation in muscle tissues of Alzheimer s disease mice and the findings provide an important basis for further exploration of the pathogenesis of Alzheimer’s disease.