目的 基于UPLC-Q-Exactive-Orbitrap-MS技術(shù)鑒定紫貝顆粒（ZBG）水提物中化學(xué)成分，并結(jié)合網(wǎng)絡(luò)藥理學(xué)和分子對接方法分析ZBG治療感染后咳嗽（PIC）的藥效物質(zhì)基礎(chǔ)及作用機制。方法 采用UPLC-Q-Exactive-Orbitrap-MS技術(shù)，表征ZBG的化學(xué)成分，并導(dǎo)入中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）、PharmMapper數(shù)據(jù)庫檢索藥物成分靶點；利用GeneCards、OMIM數(shù)據(jù)庫收集PIC相關(guān)疾病靶點，取交集后利用STRING數(shù)據(jù)庫、Cytoscape軟件構(gòu)建“ZBG成分-共有靶點”蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)并篩選核心成分與核心靶點。利用DAVID數(shù)據(jù)庫對共同靶點進(jìn)行基因本體（GO）和京都基因與基因組百科全書（KEGG）通路富集分析，借助分子對接預(yù)測核心成分和關(guān)鍵靶點的結(jié)合能力。結(jié)果 通過質(zhì)譜分析鑒定得到ZBG水提物化學(xué)成分109個，結(jié)合數(shù)據(jù)庫篩選得到ZBG治療PIC的潛在活性成分90個，與PIC治療相關(guān)的作用靶點122個。其中，蘆丁、柚皮苷、黃芩苷、異綠原酸A、香葉木苷、甘草酸等14個成分為ZBG治療PIC的核心成分，表皮生長因子受體（EGFR）、非受體酪氨酸蛋白激酶（SRC）、絲氨酸和蘇氨酸激酶1（AKT1）、磷脂酰肌醇3-激酶調(diào)控亞基（PIK3R1）、絲裂原活化蛋白激酶（MAPK8）、基質(zhì)金屬蛋白酶-9（MMP-9）等6個靶點為ZBG治療PIC的關(guān)鍵靶點。結(jié)合KEGG富集結(jié)果表明，ZBG治療PIC的機制與EGFR信號通路、MAPK信號通路和PI3K-Akt信號通路有關(guān)。分子對接結(jié)果表明ZBG中14個核心成分與6個關(guān)鍵靶點均有較好的結(jié)合活性，其結(jié)合模式主要以氫鍵為主。結(jié)論 ZBG可通過多成分、多靶點、多通路治療PIC，為后續(xù)深入揭示其藥效物質(zhì)基礎(chǔ)及作用機制提供了參考。

Objective To identify the chemical constituents in Zibei Granules (ZBG) by ultrahigh performance liquid chromatography-electrostatic field Orbitrap MS (UPLC-Q-Exactive-Orbitrap-MS), and to analyze the pharmacological basis of its efficacy in the treatment of postinfectious cough (PIC) and its mechanism of action by combining with network pharmacology and molecular docking. Methods UPLC-Q-Exactive-Orbitrap-MS was used to characterize the chemical constituents of ZBG. TCMSP and PharmMapper databases were used to screen the active components and related targets. The targets of PIC were searched using GeneCards and OMIM databases. The intersection of the main components of ZBG and the targets related to PIC was taken, and the "ZBG components-common targets" network and protein-protein interaction network were constructed by STRING database and Cytoscope software to screen for core components and core targets. Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichent analysis were performed by DAVID database. Finally, the binding ability of core components and potential key targets were predicted by molecular docking. Results A total of 109 ingredients were identified from the water extract of ZBG by UPLC-Q-Exactive-Orbitrap-MS. 90 potential active ingredients and 122 targets of ZBG for the treatment of PIC were screened out through network pharmacology analysis, of which 14 core components include rutin, naringin, baicalin and so on. The six key targets of PIC involved EGFR, SRC, AKT1, PIK3R1, MAPK8, MMP-9. The KEGG enrichment results indicated that the key mechanism of ZBG against PIC may through the synergistic regulation of EGFR, MAPK and PI3K-Akt signaling pathway. Molecular docking results showed that the core components have a good affinity with the key targets, and their binding modes were mainly based on hydrogen bonding. Conclusion ZBG has the characteristics of multi-components, multitargets and multi-pathways effects on the treatment of PIC. It would provide a scientific foundation for the further research on active components and mechanisms of ZBG in treating PIC.

R285.5

北京中醫(yī)藥大學(xué)“解碼中醫(yī)”協(xié)同攻關(guān)項目（90010961020145）