大气污染物复合暴露后血浆microRNA芯片分析

发布时间：2018-02-17 07:46

本文关键词： 大气污染物复合暴露 microRNA 神经系统发育生物信息学　出处：《环境化学》2016年12期 　论文类型：期刊论文

【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SO_2、NO_2及PM_(2.5)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(Gene ontology,GO)和信号通路(Pathway).结果提示,SO_2、NO_2及PM_(2.5)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.
[Abstract]:As miRNAs is detected in the circulatory system, plasma miRNAs can be used as a biomarker for early diagnosis of clinical diseases. In this study, we established the mice model of SO2SnNO2 and PMS-2.5), found the miRNAss in the plasma of mice after the compound exposure by miRNAs chip technology, and verified the results by real-time fluorescence quantitative PCRqRT-PCRR. Using miRandaI miRDBN miRWalk and Targetscan software to predict the target gene of miRNAs, and to analyze the gene function of target gene enrichment gene and signal pathway Pathway.The results suggest that the compound exposure of miRandaI miRDBD miRWalk and Targetscan can induce significant changes in the expression profile of miRNA in plasma of mice. Compared with the control group, 19 miRNAs were up-regulated and 7 miRNAs were down-regulated in the low concentration exposure group. In high concentration group, 64 were up-regulated and 8 down-regulated (change times were greater than 2). The results of miR-144-3p and miR-122-5p, which were the most varied in both groups, were used in bioinformatics analysis. QRT-PCR results showed that the variation trend of miR-144-3p and miR-122-5p was the same as that of microarray. Bioinformatics analysis showed that the target genes regulated by differential expression of miRNAs were significantly enriched in 30 goos (including central nervous system development). Dendritic spine and nerve spine) and two signal pathways (axonal orientation and cancer pathway) suggest that differential expression of miRNAs may be involved in the development of the central nervous system mediated by complex exposure by regulating target genes.
【作者单位】：山西大学环境与资源学院;
【基金】：国家自然科学基金(91543203,21377076) 教育部高等学校博士学科点专项科研基金(20121401110003,20131401110005)资助~~
【分类号】：R446.1;X51

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