基于生物信息技术筛选肝硬化铁死亡相关差异基因与中药预测研究

目的：采用生物信息技术筛选与肝硬化铁死亡相关的差异表达基因，并预测具有潜在治疗作用的中药及活性成分。方法：利用美国国立生物技术信息中心平台下的基因表达综合数据库（GEO） 收集肝硬化患者基因表达数据集，应用R 软件对数据集进行差异化分析，获得肝硬化的差异表达基因集（DEGs）；通过FerrDb 数据库获得铁死亡相关基因（FRGs），采用蛋白质互作（PPI） 网络分析筛选核心基因，并进行基因本体论（GO） 及京都基因与基因组百科全书（KEGG） 通路富集分析。通过Coremine Medical 数据库查找核心基因对应的中药，通过检索中药系统药理学数据库与分析平台（TCMSP） 收集中药有效活性成分和筛选核心活性成分；使用分子对接验证核心基因与核心活性成分的结合能力。结果：共筛选到与肝硬化铁死亡相关差异表达基因67 个，参与了单体代谢过程、细胞对压力的反应、含磷化合物代谢过程等，涉及p53 信号通路、谷胱甘肽代谢、FoxO 信号通路等，其中沉默信息调节因子1（SIRT1）、表皮生长因子受体（EGFR）、白细胞介素6（IL-6）、过氧化物酶体增殖活化受体α（PPARα） 和核因子红细胞2 相关因子2（NFE2L2） 5 个核心基因均在铁死亡通路中高度富集。TCMSP 预测得到丹参、枸杞子、黄芩和赤芍等17 种中药及β-谷甾醇、豆甾醇、槲皮素、山柰酚4 种关键活性成分；分子对接显示，核心基因与关键活性成分结合良好。结论：丹参、枸杞子、黄芩和赤芍等中药含有的β-谷甾醇、豆甾醇、槲皮素、山柰酚成分可以通过调控SIRT1、EGFR、IL-6、PPARα、NFE2L2 等靶点来调控铁死亡治疗肝硬化。

Study on Screening Ferroptosis-Related Differential Expression Genes of LiverCirrhosis Based on Bioinformatics and Prediction of Potential Chinese Medicine

Abstract：Objective：To screen the ferroptosis- related differential expression genes of liver cirrhosisby bioinformatics and predict the Chinese medicine and active components with potential curative effect.Methods：The Gene Expression Synthesis(GEO) database of National Center for Biotechnology Information platform was used to collect the gene expression data sets of patients with liver cirrhosis， and the Rsoftware was used to analyze the data sets to obtain the differential expression genes (DEGs) of livercirrhosis；ferroptosis- related genes (FRGs) were obtained through the FerrDb database，the core geneswere analyzed and screened by protein- protein interaction networks (PPI)， and gene ontology (GO) andKyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. UsingCoremine Medical database，the Chinese medicine corresponding to the core genes was sought，and theTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) wassearched to collect the effective active components of Chinese medicine and screen the core activecomponents； molecular docking was used to verify the binding ability of core genes to core activecomponents. Results： A total of 67 ferroptosis- related differential expression genes of cirrhosis werescreened，which played a role in monomer metabolic process，cell response to pressure，phosphoruscontainingcompound metabolic process，etc.，involving p53 signaling pathway，glutathione metabolism，and FoxO signaling pathway. Among them， five core genes of silent information regulator 1 (SIRT1)，epidermal growth factor receptor (EGFR)，interleukin 6 (IL-6)，peroxisome proliferator-activated receptorα (PPARα) and nuclear factor erythroid 2- related factor 2 (NFE2L2) were highly enriched in the ferroptosispathway. Based on TCMSP，17 kinds of Chinese medicine such as Salviae Miltiorrhizae Radix et Rhizoma，Lycii Fructus，Scutellariae Radix and Paeoniae Radix Rubra，and 4 kinds of key active components such asβ-sitosterol，stigmasterol，quercetin and kaempferol were predicted. Molecular docking showed that thecore genes were well combined with the key active components. Conclusion：The four components of β-sitosterol， stigmasterol， quercetin and kaempferol contained in Salviae Miltiorrhizae Radix et Rhizoma，Lycii Fructus， Scutellariae Radix and Paeoniae Radix Rubra can regulate ferroptosis by regulating suchtargets as SIRT1，EGFR，IL-6，PPARα and NFE2L2 in the treatment of liver cirrhosis.