目的 通过生物信息学方法筛选与铁死亡相关的特发性肺纤维化基因，分析其作用机制，并预测潜在具有治疗作用的中药及活性成分。方法 在GEO数据库搜集符合条件的特发性肺纤维化患者数据集，利用R软件对数据集进行差异分析获得差异表达基因（DEGs）。同时在FerrDb平台收集铁死亡相关基因（FRGs）。对DEGs和FRGs取交集得到铁死亡相关DEGs，进一步对铁死亡相关DEGs进行蛋白质相互作用（PPI）网络分析，筛选核心基因，并对其进行GESA通路富集分析。将核心基因提交至Coremine数据库查找对应中药，并通过TCMSP数据库找到对应中药活性成分，得到药物-活性成分网络，进一步筛选得到核心中药和核心活性成分。对核心基因与核心活性成分进行分子对接分析。结果 筛选得到723个DEGs，共收集到铁死亡相关基因487个，两者取交集得到18个铁死亡相关DEGs，通过PPI进一步筛选得到5个核心基因：环加氧酶2（PTGS2）、血红素加氧酶1（HOMX1）、白细胞介素6（IL6）、转录因子AP-1（JUN）和转录激活因子3（ATF3）。GSEA分析显示核心基因可能通过结节样受体、丝裂原活化蛋白激酶（MAPK）、信号转导子和转录激活子（JAK/STAT）、T细胞受体等信号通路发挥干预特发性肺纤维化的作用。通过预测得到丹参、干姜、人参、桑叶、桑枝等12种中药，以及4种关键活性成分槲皮素、山柰酚、谷甾醇和β-谷甾醇。分子对接显示核心基因与核心活性成分结合良好。结论 以铁死亡作为切入点，通过生物信息学分析得到特发性肺纤维化的潜在靶点，并得到潜在具有特发性肺纤维化治疗作用的中药及其活性成分。

Objective To screen the idiopathic pulmonary fibrosis (IPF) genes associated with ferroptosis by bioinformatics methods, analyze their mechanisms of action, and predict potential therapeutic traditional Chinese medicine. Methods Eligible IPF patient datasets were collected in the GEO database, and differential analysis of the datasets was performed using R software to obtain differentially expressed genes (DEGs). Ferroptosis-associated genes (FRGs) were also collected in the FerrDb platform. The DEGs and FRGs were intersected to obtain ferroptosis -related DEGs, and further protein-protein interaction (PPI) network analysis was performed to screen the core genes for ferroptosis-related DEGs and enrichment analysis of the GESA pathway was performed. The core genes were submitted to the Coremine database to find the corresponding traditional Chinese medicine, and the traditional Chinese medicine-active ingredient network map was produced after finding the corresponding traditional Chinese medicine active ingredients by TCMSP to obtain the core traditional Chinese medicine and core active ingredients. Finally, molecular docking analysis was performed between the core genes and the core active ingredients. Results 723 DEGs were screened, and 487 ferroptosis-related genes were collected. 18 ferroptosis-related DEGs were obtained by taking the intersection of the two, and five core genes were further screened by PPI: PTGS2, HOMX1, IL6, JUN, and ATF3. GSEA analysis showed that the core genes may play a role in interfering with IPF through nodule-like receptors, MAPK, JAK/STAT, T-cell receptors and other signaling pathways to intervene in IPF. Twelve Chinese herbs, including Salviae Miltiorrhizae Radix et Rhizoma, Zingiberis Rhizoma, Ginseng Radix et Rhizoma, Mori Folium and Mori Ramulus, etc. and four key active ingredients, quercetin, kaempferol, glutathione and β-sitosterol were obtained by prediction. Molecular docking showed good binding of the core genes to the core active ingredients. Conclusion Ferroptosis was used as an entry point to obtain potential biomarkers and therapeutic targets of IPF through bioinformatics analysis, and potential therapeutic herbal medicines for IPF and their active ingredients were obtained, providing new ideas for new targets and new drug development for IPF treatment.

R974;R285

国家自然科学基金资助项目（82004141）；深圳市科创委项目（JCYJ20210324131204012）；宝安区中医药发展基金会项目（2020KJCX-KTYJ-5）