应用生物信息学从铁死亡角度筛选治疗矽肺病的天然药物成分

摘要/Abstract

摘要： 目的利用生物信息学方法从铁死亡角度筛选治疗矽肺病的天然药物成分,以期为矽肺病的防治提供新的线索。方法从基因表达综合数据库（gene expression omnibus,GEO）中下载与矽肺病相关的基因表达数据集,并利用R软件对数据集行标准化处理,使用limma包对基因表达谱进行分析,得到差异表达基因。通过FerrDb数据库收集到与铁死亡相关的基因,将铁死亡相关基因与矽肺病差异表达基因提取交集。利用Webgestalt平台对交集基因进行京都基因与基因组百科全书（kyoto encyclopedia of genes and genomes,KEGG）和GO富集分析,利用STRING数据库进行交集基因的蛋白质-蛋白质相互作用（protein-protein interaction,PPI）蛋白互作网络分析,并将其导入Cytoscape软件得到核心靶点。利用SymMap平台检索靶向核心靶点的天然药物,并通过中药系统药理数据分析平台（traditional chinese medicine systems pharmacology datebase and analysis platform,TCMSP）找到天然药物的有效成分,最后进行分子对接验证。结果铁死亡相关基因与矽肺病差异表达基因取交集得到31个交集基因。GO分析表明,交集基因参与生物调节、代谢进程、多细胞进程等生物过程,KEGG功能富集分析结果显示,差异基因主要富集于铁死亡、HIF-1信号通路、糖尿病并发症中的AGE-RAGE信号通路。将交集基因导入Cytoscape软件得到5个核心靶点,槲皮素、β-谷甾醇的药物成分与核心靶点进行分子对接显示,诱导型一氧化氮合酶（recombinant nitric oxide synthase 2,NOS2）、转化生长因子Β受体Ⅰ（recombinant transforming growth factor beta receptor I,TGFBR1）与这2种药物结合能较低,结合稳定。结论槲皮素、β-谷甾醇可能是矽肺病潜在的治疗药物,NOS2、TGFBR1为核心治疗靶点,本研究结果可为研发治疗矽肺病的药物提供新的思路。

关键词: 铁死亡, 生物信息学, 矽肺病, 天然药物成分

Abstract: Objective Using bioinformatics methods to screen natural drug ingredients for the treatment of silicosis from the perspective of ferroptosis,in order to provide new clues for the prevention and treatment of silicosis. Methods The gene expression data set related to silicosis was downloaded from the GEO database,and the data set was standardized by R software. The gene expression profile was analyzed using the limma package to obtain differentially expressed genes. The genes related to ferroptosis were collected through the FerrDb database. The intersection of ferroptosis-related genes and differentially expressed genes in silicosis was performed. The KEGG and GO enrichment analysis of the intersection genes was performed using the Webgestalt platform,and the PPI protein interaction network analysis of the intersection genes was performed using the STRING database and imported into the Cytoscape software to obtain the core target. The natural drugs targeting the core targets were searched by SymMap platform,and the effective components of natural drugs were found by TCMSP. Finally,molecular docking verification was carried out. Results Totally 31 intersection genes were obtained by intersection of ferroptosis-related genes and differentially expressed genes of silicosis. GO analysis showed that the intersection genes were involved in biological processes such as biological regulation,metabolic process and multicellular process. KEGG functional enrichment analysis showed that the differential genes were mainly enriched in ferroptosis,HIF-1 signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Importing intersection genes into Cytoscape software resulted in five core targets. Quercetin and β-Sitosterol docking between the drug components of beta sitosterol and the core target showed that NOS2 and TGFBR1 had low binding energy and stable binding with these two drugs. Conclusion Quercetin and β-Sitosterol may be potential therapeutic drugs for silicosis,and NOS2 and TGFBR1 are the core therapeutic targets. The results of this study can provide new ideas for the development of drugs for the treatment of silicosis.

Key words: Ferroptosis, Bioinformatics, Silicosis, Natural pharmaceutical ingredients

中图分类号:

R135.2

高伟, 焦柯影, 何新蕾, 郝瀚. 应用生物信息学从铁死亡角度筛选治疗矽肺病的天然药物成分. [J]职业与健康, 2024, 40(14): 1889-1894.

GAO Wei, JIAO Keying, HE Xinlei, HAO Han. Application of bioinformatics in screening natural drug ingredients for the treatment of silicosis from the perspective of ferroptosis. [J]OCCUPATION AND HEALTH, 2024, 40(14): 1889-1894.

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