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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。
OBJECTIVE: To analyze differentially expressed genes (DEGs) and signal pathways related to the development and progression of silicosis by bioinformatics analysis of differentially expressed genes in blood samples from rats exposed to silica dust. METHODS: The gene expression microarray data GSE27023 from peripheral blood samples from rats exposed to silica dust was searched from a high-throughput gene expression database. DEGs were screened by paired-samples t-test and fold-to-fold method. The results of gene ontology analysis with DAVID database and Genome Encyclopedia (KEGG) pathway analysis, constructing a protein-protein interaction (PPI) network using the Interaction Genome Search Tool and Cytoscape software. Results A total of 2 767 stimuli of DEGs were screened, with 1 363 up-regulated genes and 1 404 down-regulated genes. KEGG pathway analysis showed that 39 signaling pathways such as calcium signaling pathway, neural activity receptor-ligand interaction pathway and Ras-related protein 1 signaling pathway were significantly enriched, and DEGs were most abundant, most notably calcium signaling pathway . PPI network analysis screened the highest node degree of the first 10 centromere genes encoding mitogen-activated protein kinase 14 (Mapk14), DNA-guided RNA polymerase subunit Ⅱ, erythroblastic leukemia virus oncogene homolog 4, B-lymphoblast-2 gene (Bcl-2), receptor-interacting serine / threonine kinase 4, PH domain-rich leucine-repeat-protein phosphatase 2, DNA-guided RNA polymerase subunit III, The gene-related Notch homolog 1, histone deacetylase 1, and yeast-associated switch / sucrose non-fermenter-associated stroma-associated Actin-dependent Regulatory factor subfamily A member 4, in which the upregulation of expression, Mapk14, downregulation, node degree is the highest Bcl-2. Conclusion By analyzing the peripheral blood chip data of rats with silica dust again, we screened out 39 signal pathways and 10 DEGs related to the toxicity of silica fume in rats. The calcium signaling pathway and the genes Mapk14 and Bcl- The occurrence and development of silicosis play an important role.