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[目的]应用转录组测序(RNA sequencing,RNA-seq)技术,研究苯对小鼠骨髓细胞转录组表达和信号通路的影响,为苯对小鼠骨髓细胞毒性的可能作用机制提供科学线索。[方法]将C3H/He小鼠随机分为苯暴露组[160 mg/(kg·d)]与对照组[0 mg/(kg·d)],每组10只,以皮下注射的方式染毒,每周5次,连续4周。分离小鼠的骨髓细胞,应用RNA-seq技术对苯暴露和对照组小鼠的骨髓细胞进行转录组测序,并对测序结果进行基因差异表达、基因功能与信号通路富集以及基因共表达分析。[结果]RNA-seq结果显示,苯染毒后共有227个基因的表达发生明显变化,其中122个基因下调,105个基因上调。基因功能与信号通路富集分析结果显示,这些差异基因主要富集在免疫、凋亡、代谢、氧化应激、造血谱系等功能和通路上。差异基因共表达分析显示,调控度大于10的基因有14个,其中Ccr9、Xaf1、Flt3、Cd72分别是细胞免疫、细胞凋亡、造血细胞谱系、造血细胞分化等通路上的重要基因。[结论]苯暴露可导致小鼠骨髓细胞基因表达谱发生变化,可引起小鼠骨髓细胞免疫、凋亡、代谢、氧化应激、造血谱系等功能与通路发生变化,其中Ccr9、Xaf1、Flt3、Cd72可能起关键性调控作用。
[Objective] The purpose of this study was to investigate the effect of benzene on transcriptome and signal transduction in mouse bone marrow cells by using RNA sequencing (RNA-seq) technique and to provide scientific clues for the possible mechanism of benzene toxicity on bone marrow cells in mice. [Method] C3H / He mice were randomly divided into benzene exposure group (160 mg / (kg · d)] and control group (0 mg / (kg · d) Toxic, 5 times a week for 4 weeks. The bone marrow cells of mice were isolated and the bone marrow cells of benzene exposure and control mice were sequenced by RNA-seq. The sequencing results were differentially expressed, the gene function and signaling pathway were enriched, and the co-expression of genes was analyzed. [Result] The results of RNA-seq showed that 227 genes were significantly changed after benzene exposure, of which 122 genes were down-regulated and 105 genes were up-regulated. The results of enrichment analysis of gene function and signaling pathway showed that these differentially expressed genes were mainly involved in functions and pathways of immunity, apoptosis, metabolism, oxidative stress and hematopoietic lineage. Co-expression analysis of the differentially expressed genes showed that there were 14 genes with a degree of regulation greater than 10, among which Ccr9, Xaf1, Flt3 and Cd72 were important genes in cellular immunity, apoptosis, hematopoietic lineage and hematopoietic cell differentiation. [Conclusion] Benzene exposure can lead to changes of gene expression profile of bone marrow cells in mice, which may cause changes of function and pathway of bone marrow cell immunity, apoptosis, metabolism, oxidative stress and hematopoietic lineage in mice. Cetyltrine Cd72 may play a key regulatory role.