目的 通過網(wǎng)絡(luò)藥理學(xué)及分子對接技術(shù)探討半貝丸治療支氣管炎的分子作用機制。方法 基于TCMSP數(shù)據(jù)庫結(jié)合文獻報道篩選半貝丸的有效活性成分并預(yù)測作用靶點,構(gòu)建半貝丸"成分-靶點"網(wǎng)絡(luò);運用GeneCards數(shù)據(jù)庫和OMIM數(shù)據(jù)庫獲取支氣管炎疾病靶點,構(gòu)建韋恩圖,獲得半貝丸治療支氣管炎的作用靶點;采用Cytoscape軟件構(gòu)建"疾病-活性成分"網(wǎng)絡(luò)模型;運用String平臺將共同靶點進行蛋白相互作用(PPI)網(wǎng)絡(luò)分析,通過Metascape數(shù)據(jù)庫對靶點進行基因本體(GO)功能富集及基因組百科全書(KEGG)通路富集;并采用SwissDock在線數(shù)據(jù)庫進行分子對接。結(jié)果 篩選得到半貝丸活性成分29個,共獲得潛在靶點95個,支氣管炎疾病靶點1 964個,半貝丸與支氣管炎共同靶點49個。網(wǎng)絡(luò)分析結(jié)果表明,半貝丸治療支氣管炎的關(guān)鍵靶點包括蛋白激酶(Akt1)、血管內(nèi)皮生長因子A(VEGFA)、腫瘤抑制因子P53(TP53)、半胱氨酸蛋白酶3(CASP3)、原癌基因c-Jun產(chǎn)物(JUN)、基質(zhì)金屬蛋白酶-9(MMP9)等,主要通過細(xì)胞對有機環(huán)狀化合物的反應(yīng)、凋亡信號通路、轉(zhuǎn)錄調(diào)節(jié)復(fù)合物、半胱氨酸型內(nèi)肽酶活性參與凋亡信號通路等生物過程發(fā)揮作用,KEGG富集主要涉及磷脂酰肌醇-3-激酶(PI3K)/Akt、細(xì)胞凋亡、晚期糖基化終末產(chǎn)物-晚期糖基化終末產(chǎn)物受體(AGE-RAGE)等信號通路。分子對接結(jié)果顯示半貝丸中β-谷固醇、黃芩素、豆甾醇等關(guān)鍵化合物與Akt1、VEGFA、TP53、CASP3等關(guān)鍵靶點有較好的結(jié)合能力。結(jié)論 半貝丸治療支氣管炎具有多成分、多靶點和多通路等特征。

Objective To mining the mechanism of Banbei Pills in treatment of bronchitis by network pharmacology and molecular docking and molecular docking technology. Methods To search the chemical components and targets of Banbei Pills by literature mining and TCMSP platform, and construct the "ingredient-target" network of Banbei Pills. To obtain the disease targets of bronchitis by GeneCards and OMIM database, and construct Venn diagram to obtain the targets of Banbei Pills in treatment of bronchitis. The "disease-active ingredient" network model was constructed using Cytoscape software. The common target was analyzed by using String platform for protein interaction (PPI) network analysis, and the target was enriched by GO function and KEGG pathway through Metascape database. SwissDock online database was used for molecular docking. Result A total of 29 components, 95 potential targets, 1 964 targets related to bronchitis, and 49 targets of Banbei Pills and bronchitis were obtained. The network analysis results showed that the key targets of Banbei Pills in treatment of bronchitis included Akt1, VEGFA, TP53, CASP3, JUN, and MMP9. Biological processes mainly involved cellular response to organic cyclic compound, apoptotic signaling pathway, transcription factor complex and cysteine-type endopeptidase activity involved in apoptotic signaling pathway. KEGG enrichment mainly involved PI3K/Akt, apoptosis, AGE-RAGE and other signaling pathways. The molecular docking results showed that β-sitosterol, baicalein, and sitosterol and other key compounds in Banbei Pills have better binding ability with key targets such as Akt1, VEGFA, TP53, and CASP3. Conclusion Banbei Pills in treatment of bronchitis have the characteristics of multi-component, target, and multi-pathway.

R285

河南省醫(yī)學(xué)科技攻關(guān)計劃聯(lián)合共建項目（LHGJ20210992）