文章摘要
刘建,杨莎,曾宇,等.基于生物信息学技术筛选脑出血的差异基因和药物及转录因子预测[J].安徽医药,2025,29(10):2090-2095.
基于生物信息学技术筛选脑出血的差异基因和药物及转录因子预测
Bioinformatics-based screening of differential genes and prediction of drugs and transcription factors in intracranial hemorrhage
  
DOI:10.3969/j.issn.1009-6469.2025.10.036
中文关键词: 脑出血  差异表达基因  hub基因  富集分析  中药  转录因子
英文关键词: Intracranial hemorrhage  Differentially expressed gene  Hub gene  Enrichment analysis  Traditional Chinese medi-cine  Transcription factors
基金项目:国家自然科学基金项目( 82360376)
作者单位E-mail
刘建 贵州省人民医院神经外科贵州 贵阳550005
遵义医科大学研究生院贵州遵义 563099 
 
杨莎 贵州大学医学院贵州贵阳 550025  
曾宇 贵州大学医学院贵州贵阳 550025  
孔卓 贵州医科大学研究生院贵州贵阳 550004  
王方 贵州大学医学院贵州贵阳 550025  
张继勤 贵州省人民医院麻醉科贵州贵阳550005  
王超 上海儿童医学中心贵州医院贵州贵阳 550081  
谭赢 贵州省人民医院神经外科贵州 贵阳550005
遵义医科大学研究生院贵州遵义 563099 
tanying@gz5055.com 
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中文摘要:
      目的基于生物信息学方法分析小鼠脑出血组织的基因表达,探讨影响脑出血疾病发生发展的差异表达基因及用于疾病治疗的药物预测。方法从基因表达综合( GEO)下载 GSE216607和 GSE200575进行分析,获得基因表达谱,筛选差异表达基因( DEGs)(P<0.05,|log FC|≥2)两者取交集。接着利用基因本体( GO)、京都基因和基因组数据库( KEGG)富集分析对目标基因的信号通路进行富集分析。然,后通过 STRING数据库构建蛋白质相互作用( PPI)网络。最后通过 Cytoscape软件中筛选 hub基因,对 hub基因进行实时荧光定量聚合酶链式反应( RT-qPCR)验证,将关键基因导入 Coremine Medical数据库映射出具有潜在治疗作用的药物。利用 UCSC数据库联合 JASPAR数据库预测差异表达基因相关的转录因子( TF)。结果共鉴定出 81个上调的 DEGs,GO富集分析显示其参与了白细胞迁移、细胞因子活性等。并且 KEGG富集分析中显示与细胞因子信号通路、白细胞介素( IL)-17信号通路、肿瘤坏死因子( TNF)信号通路等信号通路有关。通过 PPI网络最终筛选出 5个 hub基因 IL-1β、趋化因子配体 2(CCL2)、 C-X-C基序趋化因子配体 1(CXCL1)、金属蛋白酶组织抑制因子 1(TIMP1)、丝氨酸蛋白酶抑制因子 E1(SERPINE1)。 RT-qPCR表明与假手术组( Sham)组比较,脑出血模型组小鼠脑组织中 IL-1β、CCL2、CXCL1、TIMP1、SER-PINE1的 mRNA含量均明显上升( P<0.05)。 Coremine Medical筛选出的人参花、人参芦、人参叶、人参、茶树根等中药可能作为脑出血潜在的分子药物来源,并且筛选出马卡因、阿朴天仙子碱、灌木远志酮 A、花生四烯酸、胡萝卜苷、 β-谷甾醇、豆甾醇、吉九里香碱、谷甾醇、 9,12,15-二十二碳三烯醇、顺式 -11,14,17-二十碳三烯酸甲酯等分子可能是治疗脑出血的潜在分子药物。结论 IL-1β、CCL2、CXCL1、TIMP1、SERPINE1等基因在脑出血后表达存在差异,可能参与了脑出血后的病理机制,并且马卡因、阿朴天仙子碱、灌木远志酮 A、花生四烯酸、胡萝卜苷、 β-谷甾醇、豆甾醇、吉九里香碱、谷甾醇、 9,12,15-二十二碳三烯醇、顺式 -11,14,17-二十碳三烯酸甲酯等分子可能是治疗脑出血的潜在药物分子。
英文摘要:
      Objective To analyze the gene expression of mouse intracranial hemorrhage (ICH) tissues based on bioinformatics meth-ods, and to explore the differentially expressed genes (DEGs) affecting ICH development and drug prediction for disease treatment.Methods Gene expression profiles were obtained by downloading GSE216607 and GSE200575 from the Gene Expression Omnibus(GEO) for analysis, and DEGs were screened (P<0.05,|logFC|≥2), which were taken to be intersected. Then the signaling pathways ofthe target genes were enriched using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Next the protein-pro-tein interaction (PPI) network was constructed by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Final-ly, the hub genes were screened in Cytoscape software, and real-time quantitative polymerase chain reaction (RT-qPCR) was performed to validate the hub genes, and the key genes were imported into Coremine Medical database to map out the drugs with potential thera-peutic effects. Transcription factors (TFs) associated with DEGs were predicted using the University of California, Santa Cruz GenomicsInstitute (UCSC) Genome Browser Database in conjunction with the JASPAR database, a database of transcription factor binding profiles.Results A total of 81 up-regulated DEGs were identified, and GO enrichment analysis results showed that they were involved in leuko-cyte migration, cytokine activity and so on. Moreover, KEGG enrichment analysis results showed that they were related to cytokine signal-ing pathway, IL-17 signaling pathway, tumor necrosis factor (TNF) signaling pathway and other signaling pathways. Five hub genes, inter-leukin-1 beta (IL-1β), chemokine (C-C motif) ligand 2 (CCL2), C-X-C motif chemokine ligand 1 (CXCL1), tissue inhibitor of metallopro-teinases 1 (TIMP1), and Serpin family E member 1 (SERPINE1), were finally screened by PPI network. RT-qPCR showed that the mRNA content of IL-1β, CCL2, CXCL1, TIMP1, and SERPINE1 were significantly increased in the brain tissues of mice in the ICH model groupwhen compared with the Sham group (P<0.05). The herbal medicines such as ginseng flower, ginseng lu, ginseng leaf, ginseng, and teatree root, which were screened by Coremine Medical, may serve as potential source of molecular drugs for ICH, and screened moleculessuch as Inermin, Aposiopolamine, Frutinone A, arachidonate, alexandrin_qt, beta-sitosterol, Stigmasterol, Girinimbin, sitosterol, 9,12,15-docosatrienol, icosa-11,14,17-trienoic acid methyl ester as potential molecular drugs for the treatment of ICH.Conclusion Genes such as IL-1β, CCL2, CXCL1, TIMP1, and SERPINE1 are involved in the pathological mechanisms following intracranial hemorrhage, andthat Inermin, Aposiopolamine, Frutinone A, arachidonate, alexandrin_qt, beta-sitosterol, Stigmasterol, Girinimbin, sitosterol, 9, 12, 15-docosatrienol, and icosa-11,14,17-trienoic acid methyl ester may be potential molecular drugs for the treatment of ICH.
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