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  

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

作　　者：王雅欣 刘汶[1] 吴颖 宋思琦 刘颖初 宋瑾[1,3] 张会存 WANG Yaxin;LIU Wen;WU Ying;SONG Siqi;LIU Yingchu;SONG Jin;ZHANG Huicun(Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University,Beijing 100010,China;Beijing University of Chinese Medicine,Beijing 100029,China;Beijing Institute of Chinese Medicine,Beijing 100010,China)

机构地区：[1]首都医科大学附属北京中医医院,北京100010 [2]北京中医药大学,北京100029 [3]北京市中医药研究所,北京100010

出　　处：《新中医》2024年第3期201-208,共8页New Chinese Medicine

基　　金：国家自然科学基金项目(81873244);北京中医药科技发展资金项目(QN201624,JJ2018-30);北京市中医药研究所市财政专项课题(YJS-2023-14)。

摘　　要：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。Objective:To screen the ferroptosis-related differential expression genes of liver cirrhosis by 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 R software was used to analyze the data sets to obtain the differential expression genes(DEGs) of liver cirrhosis;ferroptosis-related genes(FRGs) were obtained through the FerrDb database,the core genes were analyzed and screened by protein-protein interaction networks(PPI),and gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed.Using Coremine Medical database,the Chinese medicine corresponding to the core genes was sought,and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was searched to collect the effective active components of Chinese medicine and screen the core active components;molecular docking was used to verify the binding ability of core genes to core active components.Results:A total of 67 ferroptosis-related differential expression genes of cirrhosis were screened,which played a role in monomer metabolic process,cell response to pressure,phosphoruscontaining compound 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 ferroptosis pathway.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.Mole

关 键 词：肝硬化 铁死亡 生物信息 差异基因 中药 

分 类 号：R575.2[医药卫生—消化系统]