[关键词]
[摘要]
目的 探讨痛风合并非酒精性脂肪肝病 (NAFLD) 的核心基因及预测潜在干预中药。方法 从 GEO 数据 库下载痛风 (GSE160170) 和 NAFLD (GSE89632) 的基因表达谱。对两个数据集的数据分别进行标准化处理,利 用 R 软件的 Limma 包筛选差异表达基因 (DEGs) ,痛风和 NAFLD 的 DEGs 取交集。通过基因本体 (GO) 和京都 基因与基因组百科全书 (KEGG) 富集分析,探讨 DEGs 的功能;使用 STRING 数据库和 Cytoscape 软件构建蛋白 质-蛋白质互作网络 (PPI) 网络。应用 cytoHubba 插件进一步筛选网络核心基因。分别在痛风 (GSE160170) 和 NAFLD (GSE89632) 数据集中验证核心基因的表达。最后利用 CoremineMedical 数据库进行其干预中药的预测。 结果 筛选获得 28 个上调基因和 60 个下调基因。其通路富集结果主要包括 NF-κB 信号通路和 TNF 信号通 路。筛选得到 4 个核心基因主要包括 BIRC3、IRF1、IL2RA、TNFSF14。预测潜在干预中药主要包括黄芪、白 术、郁金、牛膝、菝葜、夏枯草、藿香、川楝子等。结论 获得痛风合并 NAFLD 的潜在核心基因为 BIRC3、 IRF1、IL2RA、TNFSF14。其潜在干预中药包括黄芪、白术、郁金、牛膝、菝葜、夏枯草、藿香、川楝子等。 获取潜在核心基因有助于对痛风合并 NAFLD 发病机制的理解,预测干预中药有助于为临床应用中药治疗该病 提供思路。
[Key word]
[Abstract]
Objective To explore the core genes associated with gout complicated with non-alcoholic fatty liver disease (NAFLD) and predict potential therapeutic Chinese medicinals. Methods Gene expression profiles of gout (GSE160170) and NAFLD (GSE89632) were downloaded from the GEO database. First,the datasets were normalized, and differentially expressed genes (DEGs) were screened using the Limma package in R software. The intersection of DEGs from gout and NAFLD was identified. Subsequently,Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the functional implications of the DEGs. A protein- protein interaction (PPI) network was constructed using the STRING database and visualized with Cytoscape. The cytoHubba plugin was applied to further identify hub genes,whose expression levels were validated in both the gout (GSE160170) and NAFLD (GSE89632) datasets. Finally,potential Chinese medicinals interventions were predicted using the CoremineMedical database. Results A total of 28 upregulated and 60 downregulated genes were identified. Pathway enrichment analysis revealed significant associations with the NF- κB and TNF signaling pathways. Four hub genes—BIRC3,IRF1,IL2RA,and TNFSF14—were identified. Potential Chinese medicinals interventions included Astragali Radix,Atractylodis Macrocephalae Rhizoma,Curcumae Radix,Achyranthis Bidentatae Radix,Smilacis Chinae Rhizoma,Prunellae Spica,Agastachis Herba,Toosendan Fructus.Conclusion This study identified BIRC3, IRF1, IL2RA, and TNFSF14 as potential core genes in gout complicated with NAFLD. The predicted Chinese medicinals, including Astragali Radix, Atractylodis Macrocephalae Rhizoma, Curcumae Radix, Achyranthis Bidentatae Radix,Smilacis Chinae Rhizoma,Prunellae Spica,Agastachis Herba,Toosendan Fructus,may provide insights into the pathogenesis of gout-NAFLD comorbidity and offer potential therapeutic strategies for clinical application.
[中图分类号]
R285.5
[基金项目]
国家重大疑难疾病中西医临床协作项目 (20240905) ;国家自然科学基金项目 (82074377) ;天津市科技计划项目 (22KPXMRC00180) ; 风湿病 (RA、SS、痛风) 中医证侯规律研究及专家共识制定项目 (20240204011) 。