中文摘要：

随着miRNAs在循环系统中被检测出来，血浆miRNAs可以作为临床疾病早期诊断的生物标记物．为了探究交通和煤炭工业源大气污染可能对中枢神经系统产生的不良影响，本研究通过建立小鼠SO2、NO2及PM2.5复合染毒模型，利用miRNAs芯片技术发现复合暴露后小鼠血浆中发生明显变化的miRNAs，并通过实时荧光定量PCR（qRT-PCR）方法验证芯片结果，使用miRanda、miRDB、miRwalk及Targetscan软件对发生明显改变的miRNAs进行靶基因预测，分析靶基因富集的基因功能（Geneontology，GO）和信号通路（Pathway）．结果提示，SO2、NO2及PM2.5复合染毒可诱导小鼠血浆miRNA表达谱发生明显改变，低浓度暴露组与对照组相比共有19个miRNAs上调，7个miRNAs下调，高浓度组有64个上调，8个下调（变化倍数大于2），选择在两个浓度处理组中变化倍数均为最大的miR-144．3p及miR-122-5p用于生物信息学分析．qRT-PCR结果表明，miR-144-3p及miR-122-5p变化趋势与芯片一致．生物信息学分析显示差异表达miRNAs所调控的靶基因明显富集于30个GO（包括中枢神经系统发育、树突棘和神经棘等）和2条信号通路（轴突导向和癌症通路），揭示了差异表达miRNAs可能通过调控靶基因参与复合暴露介导的中枢神经系统发育．

英文摘要：

Because levels of circulating microRNAs （miRNAs） can be altered in several clinical diseases, they may serve as potential novel biomarkers. To study the impacts of air pollution caused by transportation and coal industry on the central nervous system, C57BL/6 mice were treated with two concentrations of air pollutants （SO2, NO2 and PM2.5 ） for 4 weeks. Here, we explored the differences in the profiles of plasma miRNAs in mice after co-exposure, and the microarray results were further validated by qRT-PCR. Then, the miRNAs-regulated target gene were predicted by using miranda, miRDB, miRWalk and Targetscan software. The following gene ontology and pathway of target genes were also analyzed. The results showed that the levels of plasma miRNAs （fold change 〉 2） were altered following air pollutants co-expousure, including 19 up-regulated miRNAs and 7 down-regulated miRNAs in the lower concentration group, while 64 up-regulated miRNAs and 8 down-regulated miRNAs in the higher concentration group. MiR-144-3p and miR-122-5p with the most distinct fold change in both treatment group were selected for further bioinformatics analysis, and the expression of which detected by qRT-PCR exhibited similar patterns of up or down regulation to those shown in microarray results. Bioinformatics analysis revealed that the target genes of miRNAs were significantly enriched in 30 GOs （ including central nervous system development, dendritic spine and neruon spine, pathways in cancer）, which suggested that the etc） and 2 signal pathways （axon guidance and differentially expressed miRNAs may mediate the central nervous system development through regulating target genes after S02, NO2 and PM2.5 co-exposure.