基于生物信息学探讨非酒精性脂肪性肝炎与铁死亡相关的关键基因及潜在中药预测
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R575.1

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深圳市科技创新委员会博士基础启动项目(20210795132528002);深圳市宝安区科技计划项目(20190508095339826)


Study on the Key Genes Related to Ferroptosis in Nonalcoholic Steatohepatitis Based on Bioinformatics and Prediction of Potential Chinese Medicine
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    摘要:

    目的:利用生物信息学分析来识别非酒精性脂肪性肝炎与铁死亡相关的关键基因,并预测相关作 用的中药。方法:从基因芯片数据库(GEO) 搜索并下载数据集,通过R 语言程序计算差异表达基因,并进 行基因本体(GO) 和京都基因与基因组百科全书(KEGG) 通路富集分析,利用STRING 数据库、Cytoscape 软件筛选出中心基因;通过FerrDb 数据库、基因集富集分析(GSEA) 筛选出铁死亡相关的关键基因,最后利 用HERB 数据库、COREMINE 数据库对关键基因进行中药预测,并进行分子对接。结果:分析共得出143 个 差异基因,GO、KEGG 富集主要集中在炎症反应通路;构建PPI 网络筛选出Toll 样受体4(TLR4) 等10 个基 因作为中心基因,通过FerrDb 数据库筛选关键基因TLR4,GSEA 分析提示TLR4 高表达在铁死亡基因集中高 度富集;以TLR4 为靶点预测出柴胡等8 种中药和7 种成分,7 种成分与TLR4 均能稳定结合。结论:柴胡等 中药的相关成分可能通过调控TLR4 的表达,影响肝脏细胞的铁死亡和炎症反应达到治疗非酒精性脂肪性肝炎 的作用。

    Abstract:

    Abstract:Objective:To identify the key genes related to ferroptosis in nonalcoholic steatohepatitis by bioinformatics analysis and predict the related effects of Chinese medicine. Methods: Data sets were searched and downloaded from Gene Expression Omnibus (GEO), differential expression genes were calculated by R language program, gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out, and central genes were screened by STRING database and Cytoscape software. The key genes related to ferroptosis were screened through FerrDb database and gene set enrichment analysis (GSEA). At last,the HERB database and COREMINE database were used to predict the key genes of Chinese medicine,and molecular docking was carried out. Results: A total of 143 differentially expressed genes were identified. The enrichment of GO and KEGG mainly concentrated in the inflammatory response pathway. The PPI network was constructed to screen 10 genes such as toll-like receptor 4 (TLR4) as the central gene,and the FerrDb database was used to screen the key gene TLR4. GSEA analysis showed that the high expression of TLR4 was highly enriched in the concentration of ferroptosis genes. With TLR4 as the target,8 kinds of Chinese medicines such as Bupleuri Radix and 7 kinds of components were predicted,and the 7 kinds of components could combine with TLR4 stably. Conclusion:The related components of Bupleuri Radix and other Chinese medicines may affect the ferroptosis and inflammatory reaction of liver cells by regulating the expression of TLR4 to achieve the effect of treating nonalcoholic steatohepatitis.

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欧阳子琛,李永顺,陈树超,李舒,鲁艳平,胡敬宝.基于生物信息学探讨非酒精性脂肪性肝炎与铁死亡相关的关键基因及潜在中药预测[J].新中医,2023,55(7):28-35

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  • 在线发布日期: 2023-04-12
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