目的 運(yùn)用GEO芯片、網(wǎng)絡(luò)藥理學(xué)及分子對接技術(shù)探究炙甘草湯治療肺纖維化的作用靶點(diǎn)及其潛在機(jī)制。方法 通過中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）、BATMAN-TCM、ETCM數(shù)據(jù)庫獲取炙甘草湯的化學(xué)成分靶點(diǎn)并利用Uniprot校正靶點(diǎn)；通過GEO數(shù)據(jù)庫篩選以及GeneCards、OMIM、TTD、disgenet數(shù)據(jù)庫檢索獲取肺纖維化疾病靶點(diǎn)；完成藥物成分靶點(diǎn)與疾病靶點(diǎn)的交集分析，借助Cytoscape軟件結(jié)合STRING數(shù)據(jù)庫，建立“藥物-疾病-化合物-靶點(diǎn)”關(guān)聯(lián)網(wǎng)絡(luò)，進(jìn)一步進(jìn)行蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)構(gòu)建與拓?fù)浞治?。將篩選出的共有靶點(diǎn)導(dǎo)入Metascape數(shù)據(jù)庫，進(jìn)行基因本體（GO）和京都基因與基因組百科全書（KEGG）富集分析，以篩選關(guān)鍵信號通路。最后，通過分子對接方法驗(yàn)證網(wǎng)絡(luò)藥理學(xué)的預(yù)測結(jié)果，以確保其可靠性。結(jié)果 共獲得171種炙甘草湯活性成分，與肺纖維化相關(guān)的交集靶點(diǎn)有417個(gè)。經(jīng)過PPI網(wǎng)絡(luò)的篩選，確定了19個(gè)核心靶點(diǎn)，其中排名前5的是磷酸甘油醛脫氫酶（GAPDH）、蛋白激酶B（Akt1）、腫瘤壞死因子（TNF）、白蛋白（ALB）和白細(xì)胞介素6（IL6）。GO富集分析結(jié)果顯示，炙甘草湯主要調(diào)節(jié)細(xì)胞對外界刺激的反應(yīng)、氧化應(yīng)激以及基因轉(zhuǎn)錄等關(guān)鍵生物學(xué)過程。KEGG通路富集分析揭示了包括癌癥信號通路、脂質(zhì)代謝與動脈粥樣硬化、TNF、IL-17、磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/Akt）、絲裂原活化蛋白激酶（MAPK）、AGE-RAGE和低氧誘導(dǎo)因子-1（HIF-1）在內(nèi)的多條信號通路。分子對接結(jié)果驗(yàn)證了炙甘草湯的前5種活性成分與5個(gè)關(guān)鍵蛋白的結(jié)合能均不高于-25 kJ·mol^-1，表明結(jié)合穩(wěn)定且有顯著潛力。結(jié)論 炙甘草湯中的多種活性成分可以通過多靶點(diǎn)、多信號通路針對肺纖維化發(fā)揮治療作用，為后續(xù)實(shí)驗(yàn)和臨床研究提供參考依據(jù)。

Objective To investigate the key therapeutic targets and potential mechanisms of action of Zhigancao Decoction in the treatment of pulmonary fibrosis by using GEO chip, network pharmacology and molecular docking techniques.Methods After performing an intersection analysis between the drug component targets and the disease targets, the Cytoscape software, in conjunction with the STRING database, was employed to construct a "disease-drug-compound-target" association network. Further, a proteinprotein interaction (PPI) network was constructed, and topological analysis was conducted. The screened common targets were inputted into the metascape database for GO and KEGG enrichment analysis, and the key signaling pathways were screened out. Finally, the network pharmacology results were validated using molecular docking technology.Results A total of 171 active ingredients were obtained. There were 417 targets intersecting with pulmonary fibrosis, and through PPI screening, 19 core targets were finally obtained, and the top 5 were GAPDH, Akt1, TNF, ALB, and IL6. The results of GO enrichment analysis showed that Zhigancao Decoction was mainly involved in the regulation of cellular responses to external stimuli, oxidative stress, transcriptional regulation, and other biological processes. KEGG pathway enrichment analysis revealed several signaling pathways, including cancer signaling pathways, lipid metabolism and atherosclerosis, TNF signaling pathway, IL-17 signaling pathway, PI3K/Akt signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, and HIF-1 signaling pathway. Furthermore, molecular docking results demonstrated that the binding energies of top five active components of Zhigancao Decoction with the five major targets were all below -25 kJ·mol^-1, indicating stable binding and significant potential for therapeutic application.Conclusion The various active components in Zhigancao Decoction can exert therapeutic effects on pulmonary fibrosis through multiple targets and signaling pathways, providing a reference for subsequent experiments and clinical research.

R285.5

國家自然科學(xué)基金青年項(xiàng)目（82104624）；江蘇省自然科學(xué)基金青年項(xiàng)目（BK20240731）；國家中醫(yī)藥管理局高水平中醫(yī)藥重點(diǎn)學(xué)科建設(shè)項(xiàng)目資助（國中醫(yī)藥人教函[2023]85號）；大學(xué)生創(chuàng)新創(chuàng)業(yè)訓(xùn)練國家級項(xiàng)目（202410315058Z）