锰中毒大鼠差异基因功能注释及代谢通路分析  

Functional annotation of differentially expressed genes in manganese-poisoned rats and related metabolic pathways

作　　者：田雨田 陈曾曾 郭书含 赵丽[1,2] 李震[1,2] 闫永建 Tian Yuantian;Chen Cengceng;Guo Shuhan;Zhao Li;Li Zhen;Yan Yongjian(School of Medicine and Life Sciences,University of Jinan-Shandong Academy of Medical Sciences,Shandong Academy Occupational Health and Occupational Medicine,Jinan 250062,China)

机构地区：[1]济南大学山东省医学科学院医学与生命科学学院,250062 [2]山东省医学科学院山东省职业卫生与职业病防治研究院 [3]济宁市疾病预防控制中心 [4]山东中医药大学

出　　处：《中华劳动卫生职业病杂志》2018年第12期930-934,共5页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金(81472933).

摘　　要：目的 探讨锰中毒差异基因表达的功能分类及代谢通路,为研究锰中毒机制以及基因调控防治锰中毒提供依据。 方法 选取SPF级健康雄性SD大鼠6只,按体重随机分为对照组和实验组,每组3只。实验组大鼠给予25 mg/kg MnCl2 · 4H2O,按0.2 ml/100 g进行腹腔注射,每48 h注射1次;对照组按相同注射剂量注射PBS缓冲液。暴露1个月后,将大鼠麻醉后经心脏采血法处死,冰上取大脑纹状体,提取组织RNA并建立DNA数据文库,采用全基因组测序的方法,筛选锰中毒差异基因并分别进行GO功能富集分析、Pathway富集分析,探讨差异基因可能参与的代谢途径。 结果 大鼠大脑纹状体共检测到18 439条基因,筛选出17个锰中毒差异表达基因,其中10个基因为上调基因,7个基因为下调基因;根据基因功能分析,共筛选出富集程度较高的164条基因功能分支以及26条代谢通路。基因功能较多富集在突触信号、信号传导等功能,其中富集效果最为显著的是行为功能;代谢通路中基因富集较多的通路为胞吞途径、PI3K-Akt通路以及神经活性配体-受体相互作用通路,其中PI3K-Akt信号通路与筛选出的FoxO信号通路及mTOR信号通路有同一差异基因(29517基因)富集,神经活性配体-受体相互作用通路与谷氨酸能突触通路有同一差异基因(24415基因)富集。 结论 锰中毒差异基因可能通过PI3K-Akt信号通路、mTOR信号通路或FoxO信号通路影响锰中毒易感性,并且可能参与行为学的改变。Objective To investigate the functional classification of differentially expressed genes in manganese-poisoned rats and related metabolic pathways, and to provide a reference for the study of the mechanism of manganese poisoning and gene regulation in the prevention and treatment of manganese poisoning. Methods Six healthy specific pathogen-free male Sprague-Dawley rats were randomly divided into control group and experimental group according to body weight, with 3 rats in each group. Rats in the experimental group were injected intraperitoneally with MnCl2·4H2O (25 mg/kg) at 0.2 ml/100 g once every 48 h, and the control group was injected with phosphate-buffered saline at the same dose. After one month of exposure, the rats were anesthetized and then sacrificed by cardiac puncture blood collection. The striatum was isolated on ice, and RNA was extracted to establish a DNA data library. Whole genome sequencing was used to identify the differentially expressed genes in the rats with manganese poisoning. Gene Ontology functional enrichment analysis and pathway enrichment analysis were performed to investigate the possible metabolic pathways in which the differentially expressed genes may participate. Results A total of 18439 genes were detected in the striatum of rats, and 17 differentially expressed genes were screened out. Among them, 10 genes were up-regulated, and 7 genes were down-regulated. According to gene function analysis, 164 functional branches and 26 metabolic pathways with high gene enrichment were screened out. The genes were enriched in synaptic signaling, signal transduction, etc., especially behavioral function. The metabolic pathways with high gene enrichment were endocytosis pathway, PI3K-Akt pathway, and neuroactive ligand-receptor interaction pathway, in which the PI3K-Akt pathway had enrichment of the same differentially expressed gene (29 517) as the FoxO signaling pathway and mTOR signaling pathway, and the neuroactive ligand-receptor interaction pathway had enrichment of the same differen

关 键 词：锰中毒 差异基因 功能注释 代谢通路 

分 类 号：R135.1[医药卫生—劳动卫生]