目的 基于網(wǎng)絡(luò)藥理學(xué)與分子對(duì)接方法探究齒痛消炎靈顆粒治療牙周炎的活性成分及潛在靶點(diǎn)，并探討其可能的作用機(jī)制。方法 通過TCMSP數(shù)據(jù)庫、ETCM數(shù)據(jù)庫并結(jié)合文獻(xiàn)報(bào)道篩選齒痛消炎靈顆粒潛在的活性成分及靶點(diǎn)，利用Cytoscape 3.9.1構(gòu)建"中藥-活性成分-靶點(diǎn)"的網(wǎng)絡(luò)圖；在GeneCards、TTD、OMIM、DisGeNET、DrugBank數(shù)據(jù)庫獲取牙周炎疾病相關(guān)靶點(diǎn)，利用Cytoscape 3.9.1構(gòu)建"化合物-靶點(diǎn)-疾病"相互作用網(wǎng)絡(luò)；采用STRING數(shù)據(jù)平臺(tái)構(gòu)建蛋白相互作用（PPI）網(wǎng)絡(luò)并使用Cytoscape 3.9.1軟件對(duì)其進(jìn)行拓?fù)鋵W(xué)分析；進(jìn)一步利用Metascape網(wǎng)站對(duì)篩選得到的靶點(diǎn)進(jìn)行基因本體（GO）和京都基因和基因組百科全書（KEGG）通路富集分析；選取degree值排名前5位的關(guān)鍵靶點(diǎn)和有效成分作為受體蛋白和配體小分子，使用AutoDockTools 1.5.6對(duì)配體和受體進(jìn)行分子對(duì)接，并使用Pymol將分子對(duì)接結(jié)果可視化。結(jié)果 共篩選得到齒痛消炎靈顆粒的264個(gè)潛在活性成分，得到齒痛消炎靈顆粒治療牙周炎的作用靶點(diǎn)157個(gè)；拓?fù)鋵W(xué)分析發(fā)現(xiàn)關(guān)鍵活性成分以槲皮素、山柰酚、β-谷甾醇、柚皮素、木犀草素等為主；PPI網(wǎng)絡(luò)中關(guān)鍵靶點(diǎn)為腫瘤壞死因子（TNF）、白細(xì)胞介素-6（IL-6）、白細(xì)胞介素-1β（IL-1β）、蛋白激酶B1（Akt1）、腫瘤蛋白p53（TP53）、血管內(nèi)皮生長(zhǎng)因子A （VEGFA）、半胱氨酸天冬氨酸蛋白酶-3（CASP3）、絲裂原活化蛋白激酶3（MAPK3）、表皮生長(zhǎng)因子受體（EGFR）、低氧誘導(dǎo)因子-1（HIF-1A）、前列腺素內(nèi)過氧化物合酶2（PTGS2）等。GO富集分析篩選出2 137個(gè)條目，涉及生物過程1 884條，細(xì)胞組成93條，分子功能160條；KEGG富集到基因通路206條；分子對(duì)接結(jié)果發(fā)現(xiàn)核心成分與核心靶點(diǎn)能夠較好的結(jié)合。結(jié)論 首次預(yù)測(cè)了齒痛消炎靈顆粒多成分、多靶點(diǎn)、多通路治療牙周炎的作用機(jī)制，為齒痛消炎靈顆粒的藥效物質(zhì)基礎(chǔ)研究提供了理論依據(jù)。

Objective To explore the active ingredients and potential targets of Chitong Xiaoyanling Granules in treatment of periodontitis based on network pharmacology and molecular docking technology, and to explore its possible mechanism of action. Methods Potential active ingredients and targets in Chitong Xiaoyanling Granules were screened by TCMSP database, ETCM database and literature reports. The "traditional Chinese medicine-active components-targets" network was constructed by the software of Cytoscape 3.9.1. GeneCards, TTD, OMIM, DisGeNET, and DrugBank databases were used to obtain periodontitis targets. The "compound-target-disease" interaction network was constructed by the software of Cytoscape 3.9.1. The PPI network was constructed by STRING data platform and the topological analysis was performed by Cytoscape 3.9.1. Metascape website was used to enrich and analyze the gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the selected targets. Top five key targets and active components weere selected as receptor proteins and ligand small molecules, AutoDockTools1.5.6 was used to dock ligands and receptors, and Pymol was used to visualize the molecular docking results. Result A total of 264 potential active ingredients of Chitong Xiaoyanling Granules were screened, and 157 targets of Chitong Xiaoyanling Granules were obtained for treating periodontitis. Topological analysis showed that the main active components were quercetin, kaempferol, β-sitosterol, naringenin, luteolin and so on. TNF, IL-6, IL1β, Akt1, TP53, VEGFA, CASP3, MAPK3, EGFR, HIF-1A, PTGS2 were the key targets in PPI network. 2 137 Items were screened by GO enrichment analysis, including 1 884 biological processes, 93 cellular components, and 160 molecular functions. KEGG was enriched to 206 gene pathways. Molecular docking showed that the core constituents were well bound to the core targets. Conclusion This study for the first time predicted the "multi-component, multi-target, multi-pathway" mechanism of Chitong Xiaoyanling Granules in treatment of periodontitis, which provided a theoretical basis for the material basic research of Chitong Xiaoyanling Granules efficacy.

R285

河北省自然科學(xué)基金資助項(xiàng)目（H2020206404）；河北省中醫(yī)藥管理局2020年度中醫(yī)藥類科研計(jì)劃課題（2020162）