目的 運(yùn)用網(wǎng)絡(luò)藥理學(xué)及分子對(duì)接技術(shù)探究鼻淵通竅顆粒治療慢性鼻竇炎的作用機(jī)制。方法 通過設(shè)置藥物的參數(shù)范圍在TCMSP平臺(tái)篩選鼻淵通竅顆粒的活性成分，并挖掘各個(gè)活性成分相對(duì)應(yīng)的靶點(diǎn)，在DrugBank、GeneCards、OMIM、PharmGKB和DisGeNET數(shù)據(jù)庫探索“慢性鼻竇炎”的有關(guān)靶點(diǎn)，將上述共同靶點(diǎn)導(dǎo)入String數(shù)據(jù)庫，獲得蛋白相互作用（PPI）網(wǎng)絡(luò)，利用Cytoscape 3.8.0的CytoNCA插件獲取網(wǎng)絡(luò)核心靶點(diǎn)。再利用R語言進(jìn)行基因本體論（GO）和京都基因與基因組百科全書（KEGG）通路富集分析，采用Cytoscape 3.8.0軟件進(jìn)行“藥物–活性成分–作用靶點(diǎn)–疾病”網(wǎng)絡(luò)模型構(gòu)建與分析，最后使用Sybyl軟件進(jìn)行核心靶點(diǎn)和藥物成分的分子對(duì)接并預(yù)測其結(jié)合能力。結(jié)果 鼻淵通竅顆粒有14種藥物組分，共篩選出149個(gè)活性成分，這些活性成分和慢性鼻竇炎的共同靶點(diǎn)有85個(gè)，其中核心靶點(diǎn)有7個(gè)，主要與血脂和動(dòng)脈粥樣硬化通路、人巨細(xì)胞病毒感染通路、PI3K/Akt信號(hào)通路、白細(xì)胞介素-17信號(hào)通路等相關(guān)。分子對(duì)接結(jié)果顯示，核心靶點(diǎn)與活性成分均有一定的結(jié)合活性，其中CASP3與漢黃芩素、β-谷甾醇、千層紙素A、黃芩素、刺槐素，JUN與β-谷甾醇具有較好的結(jié)合活性。結(jié)論 鼻淵通竅顆粒可能從抑制炎癥反應(yīng)、參與免疫調(diào)節(jié)、防止氧化應(yīng)激、調(diào)節(jié)脂質(zhì)代謝以及提高黏液纖毛傳輸功能等多方面發(fā)揮對(duì)慢性鼻竇炎的治療作用，為慢性鼻竇炎的治療提供理論依據(jù)和新思路。

Objective To explore the mechanism of Biyuan Tongqiao Granules in treatment of chronic sinusitis by using network pharmacology and molecular docking technology. Methods The active ingredients of Biyuan Tongqiao Granules were screened on TCMSP platform by setting the parameter range of drugs, and the corresponding targets of each active ingredient were explored. Explore "chronic sinusitis" targets at DrugBank, GeneCards, OMIM, PharmGKB, and DisGeNET databases. The above common targets were imported into the String database to obtain the protein interaction (PPI) network. The network core target was obtained by using Cytoscape 3.8.0 CytoNCA plug-in. R software was used for enrichment analysis of GO and KEGG pathways. Cytoscape 3.8.0 software was used to construct and analyze the network model of "drug-active component-target-disease". Finally, Sybyl software was used to conduct molecular docking between the core target and the drug component and predict its binding ability. Results Biyuan Tongqiao Granules contains 14 drug components, and a total of 149 active components were screened out. There are 85 common targets between these active components and chronic sinusitis, including 7 core targets, mainly including lipid and atherosclerosis pathway, human cytomegalovirus infection pathway, PI3K-Akt signaling pathway, interleukin-17 signaling pathway, etc. The results of molecular docking showed that the core targets showed certain binding activity with the active ingredients, among which CASP3 showed good binding activity with baicalein, β-sitosterol, melaletin A, baicalein, acacetin, JUN showed good binding activity with β -sitosterol. Conclusion Biyuan Tongqiao Granules may play a role in treatment of chronic sinusitis from the aspects of inhibiting inflammatory response, participating in immune regulation, preventing oxidative stress, regulating lipid metabolism and improving mucociliary transport function, providing a theoretical basis and new ideas for the treatment of chronic sinusitis.

R285

湖南省衛(wèi)生健康委科研計(jì)劃項(xiàng)目(20200004);長沙市科技計(jì)劃項(xiàng)目(kq1907010)