目的 利用網(wǎng)絡(luò)藥理學(xué)和分子對接技術(shù)，系統(tǒng)探討名中醫(yī)經(jīng)驗方三七方治療失眠的潛在作用機制。方法 通過中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）篩選三七方的藥物活性成分及其潛在靶點，并利用GeneCards、OMIM和TTD數(shù)據(jù)庫篩選失眠相關(guān)靶點，結(jié)合韋恩圖分析獲取共有靶點；使用Cytoscape軟件構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)，篩選三七方的核心靶點蛋白，并繪制藥物-成分-靶點網(wǎng)絡(luò)圖，確定主要活性成分。基于共有靶點，進行了基因本體（GO）和京都基因與基因組百科全書（KEGG）富集分析，揭示三七方治療失眠的關(guān)鍵通路。為進一步驗證分析結(jié)果，采用了Autodock軟件進行分子對接驗證。結(jié)果 三七方中的4味中藥（酸棗仁、雞血藤、小薊、三七）共篩選得到37個活性成分和233個潛在靶點，與失眠癥共有靶點82個。根據(jù)PPI網(wǎng)絡(luò)分析和藥物-成分-靶點網(wǎng)絡(luò)篩選出29個活性成分和80個失眠相關(guān)靶點，其中關(guān)鍵靶點包括白細胞介素-6（IL-6）、腫瘤壞死因子（TNF）、白細胞介素-1β（IL-1β）、細胞腫瘤抗原P53（TP53）和RAC-α絲氨酸/蘇氨酸蛋白激酶（AKT1）。核心活性成分為槲皮素、豆甾醇、β-谷甾醇和木犀草素。KEGG及GO富集分析共得到77條信號通路，主要涉及炎癥反應(yīng)、免疫應(yīng)答、血脂代謝、動脈粥樣硬化、活性氧產(chǎn)生及凋亡信號通路調(diào)控等分子機制。分子對接結(jié)果表明，核心成分與核心靶點具有較強的結(jié)合穩(wěn)定性，可通過調(diào)控多個關(guān)鍵靶點發(fā)揮作用。結(jié)論 三七方通過多成分、多靶點、多通路協(xié)同起效發(fā)揮對失眠癥治療作用，其中抗炎作用及其可能的分子機制值得關(guān)注與進一步研究。

Objective To explore the potential mechanism of Sanqifang Formula in the treatment of insomnia using network pharmacology and molecular docking technology. Methods The active ingredients of Sanqifang Formula and the potential targets were screened through the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and the insomnia related targets were screened by GeneCards, OMIM and TTD databases, and the common targets were obtained by Venn diagram analysis. Cytoscape software was used to construct the PPI network, screen the core target proteins of Sanqifang Formula, and draw the drug-component-target network diagram to determine the main active components. Based on the common targets, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to disclose the key pathways of the Sanqifang Formula in treating insomnia. For the purpose of further validating the analysis results, Autodock software was adopted for molecular docking verification.Results A total of 37 active ingredients and 233 potential targets were screened from four Chinese herbs (Ziziphi Spinosae Semen, Spatholobus Suberectus Dunn, Herba Cirsii and Panax Notoginseng), and 82 targets were shared with insomnia. According to PPI network analysis and drug-component-target network diagram, 29 active ingredients and 80 targets related to insomnia were screened. Among them, the key targets include interleukin-6 (IL-6), tumor necrosis factor (TNF), interleukin-1β (IL-1β), cellular tumor antigen P53 (TP53) and RAC-α serine/threonine protein kinase (AKT1). The core active ingredients were quercetin, stigmasterol, β-sitosterol and luteolin. A total of 77 signaling pathways were obtained by KEGG and GO enrichment analysis, which were mainly involved in molecular mechanisms such as inflammatory response, immune response, lipid metabolism, atherosclerosis, reactive oxygen species production, and apoptosis signaling pathway regulation. Molecular docking results showed that the core components had strong binding stability to the core targets and could play a role by regulating multiple key targets. Conclusion Sanqifang Formula has synergistic effect on insomnia through multi-component, multi-target and multi-pathway, and its anti-inflammatory effect and possible molecular mechanism deserve attention and further study.

R285.5

上海市2022年度“科技創(chuàng)新行動計劃”生物醫(yī)藥科技支撐專項項目（22S21900800，22S21900700）;國家中醫(yī)藥管理局第七批全國老中醫(yī)藥專家學(xué)術(shù)經(jīng)驗繼承工作項目（國中醫(yī)藥人教函〔2022〕76號）;國家中醫(yī)藥管理局2022年全國名老中醫(yī)藥專家傳承工作室建設(shè)項目“蔣健全國名老中醫(yī)藥專家傳承工作室”（國中醫(yī)藥人教函〔2022〕75號）;國家中醫(yī)藥管理局中醫(yī)藥傳承與創(chuàng)新“百千萬”人才工程（岐黃工程）岐黃學(xué)者項目（國中醫(yī)藥辦人教函〔2019〕62號）;上海市衛(wèi)生和計劃生育委員會上海市名老中醫(yī)學(xué)術(shù)經(jīng)驗研究工作室建設(shè)項目（SHGZS-2017024）