目的 運(yùn)用網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接技術(shù)研究益氣開秘方治療便秘的作用靶點(diǎn)及效應(yīng)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(tái)收集篩選益氣開秘方中組方藥材的有效活性成分及對(duì)應(yīng)靶點(diǎn)，利用GeneCards、OMIM、PharmGKB、TTD及DrugBank數(shù)據(jù)庫獲取疾病靶點(diǎn)；利用R軟件4.1.1篩選成分和疾病的交集靶點(diǎn)，利用STRING數(shù)據(jù)庫（version 11.5）和Cytoscape 3.8.2軟件構(gòu)建蛋白質(zhì)–蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)；運(yùn)用R軟件4.1.1進(jìn)行基因本體（GO）功能及京都基因與基因組百科全書（KEGG）通路富集分析；運(yùn)用Autodock軟件對(duì)關(guān)鍵作用靶點(diǎn)和活性成分進(jìn)行分子對(duì)接，驗(yàn)證網(wǎng)絡(luò)分析結(jié)果。結(jié)果 益氣開秘方主要包含68個(gè)活性成分，活性成分對(duì)應(yīng)靶點(diǎn)170個(gè)；便秘疾病靶點(diǎn)共1 586個(gè)；益氣開秘方與便秘的交集靶點(diǎn)基因共68個(gè)。PPI分析出核心靶點(diǎn)為絲裂原活化蛋白激酶1（mitogen-activated protein kinase 1，MAPK1）、MAPK3、蛋白激酶B1（AKT1）等；GO功能注釋得到生物學(xué)過程條目1 825條（如衰老、平滑肌細(xì)胞增殖、肽基-絲氨酸磷酸化等），細(xì)胞組成條目60條（如膜筏、膜微結(jié)構(gòu)域、絲氨酸/蘇氨酸蛋白激酶復(fù)合物等）、分子功能條目157條（如磷酸酶結(jié)合、內(nèi)肽酶活力、絲氨酸肽鏈內(nèi)切酶活性等）；KEGG通路富集分析確定了168條益氣開秘方治療便秘作用靶點(diǎn)的通路（如PI3K/AKT信號(hào)通路、細(xì)胞衰老、MAPK信號(hào)通路、肌動(dòng)蛋白細(xì)胞骨架調(diào)節(jié)等）；分子對(duì)接提示MAPK1、MAPK3、AKT1與主要核心成分（槲皮苷、木犀草素以及山柰酚）的結(jié)合能均<—20 kJ/mol。結(jié)論 益氣開秘方中的槲皮苷、木犀草素以及山柰酚等活性成分可能通過與MAPK1、MAPK3、AKT1等靶點(diǎn)進(jìn)而調(diào)控MAPK信號(hào)通路以及磷酸肌醇-3-激酶（PI3K）/AKT信號(hào)通路等信號(hào)通路起到治療便秘的作用。

To study the target and mechanisms of Yiqi Kaimi Prescription in treatment of constipation based on network pharmacology and molecular docking. Methods The effective active components and corresponding targets of Yiqi Kaimi Prescription were collected and screened via TCMSP. The disease targets were obtained from the GeneCards, OMIM, PharmGKB, TTD and DrugBank databases. The intersection targets of components and diseases were screened by R software 4.1.1, and the protein interaction network was constructed by the STRING database (version 11.5) and Cytoscape 3.8.2. R software 4.1.1 was used for GO biological function analysis and KEGG pathway analysis. The key targets and active components were docked by Autodock software to verify the network analysis results. Results Yiqi Kaimi Prescription primarily contained 68 active ingredients, and the active ingredients corresponded to 170 targets. There were 1 586 targets for constipation, and 68 target genes for the intersection of Yiqi Kaimi Prescription and constipation. PPI network analysis showed that the core targets were MAPK1, MAPK3 and AKT1. GO functional analysis showed 1 825 biological processing items (such as aging, smooth muscle cell proliferation, peptide serine phosphorylation, etc.), 60 cell composition items (such as membrane raft, membrane microdomain, serine/threonine protein kinase complex, etc.), and 157 molecular functional items (such as phosphatase binding, endopeptidase activity, serine endopeptidase activity, etc.). KEGG pathway enrichment analysis identified 168 pathways (such as PI3K/AKT signaling pathway, cell senescence, MAPK signaling pathway, actin cytoskeleton regulation, etc.) for the treatment of constipation; Molecular docking showed that the binding energies of MAPK1, MAPK3 and AKT1 with the central core components (quercetin, luteolin, and kaempferol) were <−20 kJ/mol. Conclusion Quercetin, luteolin and kaempferol in Yiqi Kaimi Prescription may regulate cellular aging, MAPK signaling pathway and PI3K/AKT signaling pathway by interacting with MAPK1, MAPK3 and AKT1.

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國家中醫(yī)藥管理局關(guān)于開展全國中醫(yī)學(xué)術(shù)流派傳承工作室第二輪建設(shè)項(xiàng)目（國中醫(yī)藥人教函[2019]62號(hào)）；上海市臨床重點(diǎn)專科項(xiàng)目（shslczdzk04301）；中醫(yī)藥流派發(fā)展高地建設(shè)—海派中醫(yī)流派傳承延伸計(jì)劃項(xiàng)目[ZY（2021—2023）-0209]；上海中醫(yī)藥大學(xué)杏林學(xué)者及追蹤計(jì)劃項(xiàng)目（RC-2017-02-08）；國家自然科學(xué)基金項(xiàng)目（81603625，82174373）