长期农药暴露的毒性作用及关键基因发掘  

Toxic effects of long-term pesticides exposure and key gene discovery

作　　者：蒋斌杰[1] 窦建瑞 韩磊[3,4] 张恒东 张锋[3,4] 刘炘 Jiang Binjie;Dou Jianrui;Han Lei;Zhang Hengdong;Zhang Feng;Liu Xin(Department of Occupational Disease Control,Wujin Center for Disease Control and Prevention of Changzhou,Changzhou 213164,China;Scenic Area Division,Yangzhou Center for Disease Control and Prevention,Yangzhou 225007,China;Institute of Occupational Disease Prevention,Jiangsu Provincial Center for Disease Control and Prevention,Nanjing 210028,China;Jiangsu Preventive Medical Association,Nanjing 210028,China)

机构地区：[1]常州市武进区疾病预防控制中心职业病防制科,常州213164 [2]扬州市疾病预防控制中心景区分中心,扬州225007 [3]江苏省疾病预防控制中心职业病防治所,南京210028 [4]江苏省预防医学会,南京210028

出　　处：《中华劳动卫生职业病杂志》2022年第9期641-648,共8页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：扬州市科技发展计划项目(YZ2020094);江苏省卫生健康委医学科研项目(N2020178)。

摘　　要：目的运用生物信息学方法挖掘农药慢性暴露诱导的差异表达基因(DEGs)及其富集的信号通路,探索其潜在致病机制和关键基因。方法于2021年7月,从基因表达综合数据库(GEO)中下载与农药毒效应相关的高通量基因表达谱数据,样本来源为长期接触农药的美洲男性农场工人和其他行业工人,获取DEGs;利用R软件clusterProfiler包对所选择的DEGs进行GO、KEGG及基因集富集分析(GSEA);采用STRING、Cytoscape等工具对其进行蛋白质相互作用网络的构建及可视化分析;借助MCODE及Cytohubba等分析得到基因功能模块,从而筛选出核心基因。结果共筛选出GSE30335数据集的DEGs 189个,其中上调基因101个,下调基因88个。GO、KEGG及GSEA结果显示,DEGs主要富集于神经元投射发育调控、运动调节、核糖体蛋白合成等生物学功能及以帕金森病为代表的复杂神经系统疾病相关的通路上。综合筛选发现,KLF1为农药暴露的核心基因,其差异表达倍数为0.456(t=-3.82,P=0.021)。结论长期农药暴露可造成接触人群多个基因的差异表达,可能通过下调KLF1并经由其介导的一系列生物学途径参与神经系统的病理学改变。Objective Bioinformatics methods were used to mine differentially expressed genes(DEGs)and enriched signal pathways induced by chronic pesticide exposure,and explore its potential pathogenic mechanisms and key genes.Methods In July 2021,high-throughput gene expression profile data related to pesticide toxicity was downloaded from Gene Expression Omnibus(GEO)database to obtain DEGs.The samples were from American male farm workers who had been exposed to pesticides for a long time and other industry workers.The functional enrichment analysis of GO,KEGG and Geme Set Enrichment Analysis(GSEA)were performed by R package clusterProfiler.STRING,Cytoscape and other tools were applied to construct and visualize the protein interaction network.With the help of MCODE and Cytohubba plugins,gene function modules were obtained,and hub gene was screened out.Results 189 DEGs were screened from GSE30335 dataset,including 101 up-regulated genes and 88 down-regulated genes.The results of GO,KEGG and GSEA were mainly enriched in biological functions such as regulation of neuron projection development,regulation of locomotion,ribosomal protein synthesis,and pathways related to complex nervous system diseases such as Parkinson's disease.And the comprehensive screening showed that KLF1 was the hub gene of pesticide exposure,with a fold change of 0.456(t=-3.82,P=0.021).Conclusion Long term exposure to pesticides results in the differential expression of multiple genes in the exposed population,which may be involved in the pathological changes of nervous system by down regulating KLF1 and related biological pathways.

关 键 词：农药 基因表达综合数据库 生物信息学分析 差异表达基因 关键基因 

分 类 号：R994[医药卫生—毒理学]