目的 通過(guò)生物信息學(xué)方法篩選與鐵死亡相關(guān)的特發(fā)性肺纖維化基因，分析其作用機(jī)制，并預(yù)測(cè)潛在具有治療作用的中藥及活性成分。方法 在GEO數(shù)據(jù)庫(kù)搜集符合條件的特發(fā)性肺纖維化患者數(shù)據(jù)集，利用R軟件對(duì)數(shù)據(jù)集進(jìn)行差異分析獲得差異表達(dá)基因（DEGs）。同時(shí)在FerrDb平臺(tái)收集鐵死亡相關(guān)基因（FRGs）。對(duì)DEGs和FRGs取交集得到鐵死亡相關(guān)DEGs，進(jìn)一步對(duì)鐵死亡相關(guān)DEGs進(jìn)行蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)分析，篩選核心基因，并對(duì)其進(jìn)行GESA通路富集分析。將核心基因提交至Coremine數(shù)據(jù)庫(kù)查找對(duì)應(yīng)中藥，并通過(guò)TCMSP數(shù)據(jù)庫(kù)找到對(duì)應(yīng)中藥活性成分，得到藥物-活性成分網(wǎng)絡(luò)，進(jìn)一步篩選得到核心中藥和核心活性成分。對(duì)核心基因與核心活性成分進(jìn)行分子對(duì)接分析。結(jié)果 篩選得到723個(gè)DEGs，共收集到鐵死亡相關(guān)基因487個(gè)，兩者取交集得到18個(gè)鐵死亡相關(guān)DEGs，通過(guò)PPI進(jìn)一步篩選得到5個(gè)核心基因：環(huán)加氧酶2（PTGS2）、血紅素加氧酶1（HOMX1）、白細(xì)胞介素6（IL6）、轉(zhuǎn)錄因子AP-1（JUN）和轉(zhuǎn)錄激活因子3（ATF3）。GSEA分析顯示核心基因可能通過(guò)結(jié)節(jié)樣受體、絲裂原活化蛋白激酶（MAPK）、信號(hào)轉(zhuǎn)導(dǎo)子和轉(zhuǎn)錄激活子（JAK/STAT）、T細(xì)胞受體等信號(hào)通路發(fā)揮干預(yù)特發(fā)性肺纖維化的作用。通過(guò)預(yù)測(cè)得到丹參、干姜、人參、桑葉、桑枝等12種中藥，以及4種關(guān)鍵活性成分槲皮素、山柰酚、谷甾醇和β-谷甾醇。分子對(duì)接顯示核心基因與核心活性成分結(jié)合良好。結(jié)論 以鐵死亡作為切入點(diǎn)，通過(guò)生物信息學(xué)分析得到特發(fā)性肺纖維化的潛在靶點(diǎn)，并得到潛在具有特發(fā)性肺纖維化治療作用的中藥及其活性成分。

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

國(guó)家自然科學(xué)基金資助項(xiàng)目（82004141）；深圳市科創(chuàng)委項(xiàng)目（JCYJ20210324131204012）；寶安區(qū)中醫(yī)藥發(fā)展基金會(huì)項(xiàng)目（2020KJCX-KTYJ-5）