基于失眠–炎症相关基因共表达网络探讨失眠与炎症的相关性及机制

To Explore the Correlation and Mechanism between Insomnia and Inflammation Based on the Co-Expression Network of Insomnia and Inflammation Related Genes

摘要: 目的：运用生物信息学方法，分析原发性失眠差异基因与炎症相关基因和相关富集通路，进一步通过共表达网络与抗失眠药物的关系深入探讨其与治疗药物的关系。方法：使用GEO2R对数据库中筛选出的原发性失眠芯片数据进行差异基因表达分析，并与炎症相关基因取交集。对差异基因进行本体论富集分析和功能富集分析，利用String数据库进行蛋白网络互作分析，并使用Cytoscape软件获取关键基因。最后，利用CTD数据库将关键基因与失眠药物相关基因进行比对。结果：与健康对照相比，原发性失眠患者有2382个差异表达基因，主要涉及细胞因子介导的信号通路、对细菌来源分子的反应和对脂多糖的反应等生物过程。蛋白互作网络的分析筛选出IL10、CCL5、IL18、IL1B等10个关键基因。通过CTD数据库，发现有CCL5、CCR7、IL10、IL18、IL1B等6个关键基因与褪黑素相互作用。结论：原发性失眠患者血清中存在明显的基因表达差异，褪黑素治疗失眠的机制可能与NLRP3相关。

Abstract: Objective: To analyze the differentially expressed genes and inflammation-related genes and relat-ed enriched pathways in primary insomnia using bioinformatics methods, and to further explore the relationship between anti-insomnia drugs and therapeutic drugs through the co-expression network. Methods: GEO2R was used to analyze the differential gene expression of primary insomnia microarray data screened from the database, and the intersection with inflammation-related genes was taken. Ontology enrichment analysis and functional enrichment analysis were performed on the differentially expressed genes. Protein network interaction analysis was performed using String database, and the key genes were obtained using Cytoscape software. Finally, the key genes were aligned with insomnia drug-related genes using the CTD database. Results: Compared with healthy controls, patients with primary insomnia had 2382 differentially expressed genes, which were mainly involved in biological processes such as cytokine-mediated signaling pathways, response to bacterial-derived molecules, and response to lipopolysaccharide. Ten key genes including IL10, CCL5, IL18 and IL1B were screened by protein interaction network analysis. Through the CTD data-base, six key genes were found to interact with melatonin, including CCL5, CCR7, IL10, IL18, and IL1B. Conclusion: There are significant gene expression differences in the serum of patients with primary insomnia, and the mechanism of melatonin in the treatment of insomnia may be related to NLRP3.