摘要
目的 基于生物信息学方法分析异氟烷麻醉诱发脑损伤的核心基因及机制.方法 从GPL85生成的GEO数据库中下载异氟烷麻醉数据集GSE358和GSE359配置文件.进行去批次化处理,筛选差异表达基因(DEGs),进行基因本体(GO)注释及京都基因与基因组百科全书(KEGG)通路分析,构建和分析蛋白质-蛋白质相互作用(PPI)网络,对PPI网络中寻找到的核心基因绘制基因表达量热图,通过毒物基因组学数据库(CTD)分析找到与核心基因最相关的疾病.结果 共鉴定出500个DEGs.GO分析结果:生物学过程分析中,主要富集在对外源性刺激反应、对缺氧反应、凋亡以及炎症反应过程;细胞组成分析中,主要富集在细胞质、细胞外空间、神经元投射;分子功能分析中,主要富集在蛋白结合、转录调控区序列特异性DNA结合.KEGG分析:主要富集在磷脂酰肌醇3激酶/蛋白激酶B信号通路、神经活性配体-受体相互作用、Toll样受体信号通路、细胞凋亡、环磷酸腺苷信号通路.PPI网络获得了 6个核心基因:干扰素γ(IFN-γ)、Toll样受体4(TLR4)、核因子κB抑制因子α(NFKBIA)、白细胞介素-1α(IL-1α)、原癌基因Fos和CCAAT增强子结合蛋白β(CEBPB).CTD分析发现核心基因与神经系统疾病、脑损伤、痛觉过敏、药物相关的副作用和不良反应、神经变性等有关.推断分数可以反映基因与疾病相关的程度,其中IFN-γ、IL-1α、Fos在脑损伤方面推断分数较高.结论 IFN-γ、IL-1α、Fos、TLR4、NFKBIA和CEBPB是异氟烷麻醉诱发脑损伤有关的6个核心基因,这些基因可能在免疫和炎症反应等方面发挥重要作用.
Abstract
Objective To analyse the core genes and mechanisms of brain injury induced by isoflu-rane using the bioinformatics analysis.Methods The GSE358 and GSE359 isoflurane anesthesia data set were downloaded from the GEO database.Debatch processing,screening of differentially expressed genes(DEGs),construction and analysis of protein-protein interaction network,and functional enrichment analy-sis were performed.The gene expression heat map was plotted,and the diseases most related to the core genes were found by Comparative Toxicogenomics Database analysis.Results A total of 500 DEGs were identified.According to the results of Gene Ontology analysis,they were mainly enriched in the response to foreign stimuli,the response to hypoxia,the apoptotic process,and the inflammatory response in the Biolog-ical Process analysis.In Cellular Component analysis,they were mainly enriched in the cytoplasm,extracel-lular space,and neuronal projections.In Molecular Function analysis,they focused on protein binding and sequence specific DNA binding in transcriptional regulatory regions.In Kyoto Encyclopedia of Genes and Genomes analysis,they were mainly enriched in phosphatidylinositol 3-kinase/protein kinase B signaling pathway,neuroactive ligand-receptor interaction,Toll-like receptor(TLR)signaling pathway,apoptosis and cAMP signaling pathway.Six core genes(interferon gamma[IFN-γ],TLR4,nuclear factor kappa B inhibitor alpha[NFKBIA],interleukins-1α[IL-1α],proto-oncogene fos[Fos]),CCAAT enhancer binding proteinβ[CEBPB])were obtained by protein-protein interaction network.Comparative Toxicogenomics Database analysis revealed that core genes(IFN-y,IL-1α,Fos)were associated with neurological disorders,brain in-jury,hyperalgesia,drug-related side effects and adverse reactions,neurodegeneration,etc.The inference score could reflect the degree of association between the gene and the disease,among which IFN-γ,IL-1αand Fos had higher inference scores in brain damage.Conclusions IFN-γ,IL-1α,Fos,TLR4,NFKBIA and CEBPB are six core genes associated with isoflurane-induced brain injury,and these genes may play im-portant roles in immune and inflammatory responses.
基金项目
天津市科技计划(20JCZDJC00810)
天津市卫生健康科技项目(TJWJ2023MS027)
天津市医学重点学科(专科)建设项目(TJYXZDXK-042A)
NETL
NSTL
万方数据