抑郁症小鼠海马组织差异表达炎症因子基因筛选及生物信息学分析  

Screening and bioinformatics analysis of differentially expressed inflammatory cytokine genes in hippocampi of mice with depression

作　　者：邵青 袁东亮 王娜[1] 阎得胜[1] 张晓红[1] 张辉[1] 权伟[1,2] SHAO Qing;YUAN Dongliang;WANG Na;YAN Desheng;ZHANG Xiaohong;ZHANG Hui;QUAN Wei(Xi’an Mental Health Center,Xi’an 710199,China;不详)

机构地区：[1]西安市精神卫生中心,西安710199 [2]空军军医大学 [3]空军军医大学唐都医院

出　　处：《山东医药》2021年第8期42-45,共4页Shandong Medical Journal

基　　金：陕西省自然科学基础研究计划项目(2020JM-701);西安市科技局医学项目(2019115113YX006SF039-11);西安市“科技+”行动计划-医学研究项目(J201803045,J201902026)。

摘　　要：目的筛选抑郁症小鼠海马组织中差异表达的炎症因子基因,并进行生物信息学分析。方法将12只C57小鼠分为对照组和抑郁症组,每组6只。抑郁症组通过慢性不可预知温和应激模型制备小鼠抑郁症模型,对照组不造模。取两组海马组织,采用实时定量PCR检测84个炎症因子基因。采用GeneSpring GX11.5.1软件分析基因芯片数据,获取两样本信号强度比值(Ratio),将Ratio>2或<0.5作为有表达差异,Volcano Plot筛选差异表达基因。对差异表达基因进行GO生物过程(GO-BP)富集分析和KEGG通路分析。通过对GO-BP分析及KEGG通路分析结果进行交集,筛选目标差异表达基因。结果与对照组相比,抑郁症组中差异表达的细胞因子基因有6个,表达上调的3个基因分别为CXCL5、BMP2、IL10RA,表达下调的3个基因分别为CCL12、IL5、IL1A。差异表达基因主要参与白细胞迁移、白细胞趋化性及免疫系统过程等生物过程的调控,参与细胞因子与细胞因子受体相互作用通路、趋化因子信号转导通路及IL-17信号转导通路等。共筛选出4个目标差异基因,为CXCL5、BMP2、IL1A、CCL12基因。结论抑郁症小鼠海马组织中差异表达的炎症因子基因主要为CXCL5、BMP2、IL1A、CCL12等,这些炎症因子基因可能通过调控多种生物过程和多条信号通路参与抑郁症的发病。Objective To screen out the differentially expressed inflammatory cytokine genes in hippocampi of mice with depression and to analyze their relevant bioinformatics.Methods Twelve C57 mice were randomly divided into the control group and the depression group,with 6 in each.The depression models were built in mice by using chronic unpredictable mild stress models,and the mice in the control group were not treated.The hippocampi of the two groups were collected,and 84 inflammatory cytokine genes were detected by real-time quantitative PCR.GeneSpring GX11.5.1 software was employed to analyze the microarray data,and the ratio of signal intensity(Ratio)of the two samples was determined;the differentially expressed genes were screened out through Volcano Plot by taking the Ratio>2 or<0.5 as the genes with differential expression.The differentially expressed genes were analyzed by GO biological process(GO-BP)enrichment analysis and KEGG pathway analysis.Target differentially expressed genes were screened out by intersecting the results achieved by GO-BP analysis and KEGG pathway analysis.Results There were 6 cytokine genes differentially expressed in the depression group as compared with those of the control group,including three up-regulated genes CXCL5,BMP2 and IL10RA,and three down-regulated genes CCL12,IL5 and IL1A.Differentially expressed genes were largely involved in the process of regulating leukocyte migration,leukocyte chemotaxis and immune system processes.Moreover,the genes participated in the cytokine-cytokine receptor interaction pathway,chemokine signal transduction pathway,as well as IL-17 signal transduction pathway.Four target differential genes CXCL5,BMP2,IL1A and CCL12 were screened out.Conclusion The inflammatory cytokine genes differentially expressed in the hippocampi of depressed mice primarily include CXCL5,BMP2,IL1A,CCL12 and so on,which may be involved in the pathogenesis of depression by regulating a wide range of biological processes and participating in multiple signaling pathways.

关 键 词：抑郁症 海马组织 炎症因子 基因芯片 生物信息学 

分 类 号：R749.4[医药卫生—神经病学与精神病学]