中文摘要：

目的 采用生物信息学方法,对染矽尘大鼠周围血标本的芯片进行差异基因表达谱分析,筛选与矽肺发生发展相关的潜在差异表达基因（DEGs）和信号通路.方法 从高通量基因表达数据库检索染矽尘大鼠的周围血样品基因表达微阵列芯片数据集GSE27023,采用配对样本t检验和倍比法筛选DEGs,采用DAVID数据库进行基因本体分析和京都基因与基因组百科全书（KEGG）通路分析,采用相互作用基因库检索工具和Cytoscape软件构建蛋白质-蛋白质相互作用（PPI）网络.结果 共筛选出2 767个刺激反应DEGs,上调基因1 363个,下调基因1 404个.KEGG通路分析结果显示,钙信号通路、神经活性的受体-配体相互作用通路和Ras相关蛋白1信号通路等39条信号通路被显著富集,DEGs富集最多、最显著的是钙信号通路.PPI网络分析筛选出节点度最高的前10个中心蛋白编码基因分别是丝裂原活化蛋白激酶14（Mapk14）、DNA指导的RNA聚合酶Ⅱ亚基、成红细胞白血病病毒癌基因同源物4、B淋巴细胞瘤-2基因（Bcl-2）、受体相互作用的丝氨酸/苏氨酸激酶4、PH域富含亮氨酸重复蛋白磷酸酶2、DNA指导的RNA聚合酶Ⅲ亚基、神经源性基因Notch同源蛋白1、组蛋白去乙酰化酶1、酵母交换型转换/蔗糖不发酵相关基质关联肌动蛋白依赖性调节因子亚家族A成员4,其中表达上调、节点度最高的是Mapk14,表达下调、节点度最高的是Bcl-2.结论 通过再次分析大鼠染矽尘后周围血芯片数据,筛选出与大鼠染矽尘毒性反应相关的39条信号通路和10个DEGs;钙信号通路和基因Mapk14、Bcl-2可能在大鼠矽肺的发生发展过程中发挥重要作用.

英文摘要：

Objective To analyze the difference in gene expression profiles and screen silicosis development related differentially expressed genes （DEGs） and signaling pathways in peripheral blood specimens of rats exposed to silica dust using bioinformatics and gene chip.Methods GSE27023 gene expression profiles of peripheral blood samples of rats exposed to silica dust were downloaded from Gene Expression Omnibus database.After screening of the DEGs through paired-sample t-test and fold change method,DEGs related to rats exposed to silica dust was performed by Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis.The protein-protein interaction （PPI） network was constructed with the Search Tool for the Retrieval of Interacting Genes database and visualized using the software Cytoscape.Results Of the 2 767 DEGs screened,1 363 were up-regulated and 1 404 were down-regulated.KEGG pathway enrichment analysis showed that 39 signaling pathways,such as the calcium signaling pathway,neuroactive ligand-receptor interaction,Ras-related protein 1 signaling pathway,were significantly enriched.DEGs enrichment and significance reached the highest level in the calcium signaling pathway.PPI network and module analysis suggested that mitogen-activated protein kinase 14 （Mapk14）,DNA-directed RNA PolymeraseⅡ,V-erb-a erythroblastic leukemia viral oncogene homolog 4,B-cell lymphoma-2 （Bcl-2）,receptor interacting serine/threonine kinase 4,PH domain leucine-rich repeat protein phosphatase 2,DNA-directed RNA polymerase Ⅲ,neurogenic locus notch homolog protein 1,histone deacetylase 1,yeast switch in mating type/Sucrose non fermentation related,matrix associated,actin dependent regulator of chromatin,subfamily a,member 4 were top 10 hub-proteins.Mapk14 had the highest node degree in up-regulated DEGs,and Bcl-2 had the highest node degree in down-regulated DEGs.Conclusion We found 39 signaling pathways and 10 DEGs that are related to toxicity caused by exp