目的 基于網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接技術(shù)探討復(fù)方丹參滴丸治療心絞痛的潛在分子機(jī)制。方法 通過中藥系統(tǒng)網(wǎng)絡(luò)藥理學(xué)數(shù)據(jù)庫與分析平臺(tái)（TCMSP）檢索復(fù)方丹參滴丸的活性成分，利用GeneCards、Disgnet和TTD數(shù)據(jù)庫檢索心絞痛疾病相關(guān)靶點(diǎn)，通過String數(shù)據(jù)庫和Metascape開放平臺(tái)對(duì)復(fù)方丹參滴丸與心絞痛的交集靶點(diǎn)進(jìn)行京都基因與基因組百科全書（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析及基因本體論（gene ontology，GO）注釋。采用SYBYL2.1軟件的Surflex-Dock模塊對(duì)篩選的核心成分和核心靶點(diǎn)進(jìn)行分子對(duì)接。結(jié)果 從復(fù)方丹參滴丸中篩選出76種活性化合物，涉及500個(gè)潛在靶點(diǎn)。復(fù)方丹參滴丸成分靶點(diǎn)與心絞痛疾病靶點(diǎn)取交集，共獲得457個(gè)交集靶點(diǎn)；復(fù)方丹參滴丸治療心絞痛作用靶標(biāo)的蛋白相互作用（PPI）網(wǎng)絡(luò)中共包含158個(gè)節(jié)點(diǎn)，其中重要的靶點(diǎn)有STAT3、TP53、AKT1、JUN、MAPK1、HSP90AA1等。復(fù)方丹參滴丸通過調(diào)控炎癥反應(yīng)、凋亡信號(hào)通路、積極調(diào)節(jié)細(xì)胞遷移等GO生物過程，參與流體剪切應(yīng)力與動(dòng)脈粥樣硬化、PI3K-Akt信號(hào)通路、MAPK信號(hào)通路、HIF-1信號(hào)通路、TNF信號(hào)通路、IL17信號(hào)通路等信號(hào)通路，發(fā)揮治療心絞痛的作用。分子對(duì)接結(jié)果表明篩選得到的活性成分與靶點(diǎn)有較強(qiáng)的結(jié)合。結(jié)論 運(yùn)用網(wǎng)絡(luò)藥理學(xué)研究方法推測(cè)出復(fù)方丹參滴丸治療心絞痛的潛在分子機(jī)制及作用靶點(diǎn)，分子對(duì)接驗(yàn)證了篩選的關(guān)鍵活性成分與重要靶點(diǎn)具有較強(qiáng)的結(jié)合活性。

Objective To explore the potential molecular mechanism of Compound Danshen Dripping Pills in treatment of angina pectoris based on network pharmacology and molecular docking technology. Methods The active ingredients of Compound Danshen Dropping Pills were retrieved through the Traditional Chinese Medicine System Network Pharmacology Database and Analysis Platform (TCMSP), and the angina pectoris-related targets were retrieved using GeneCards, Disgnet and TTD databases. KEGG enrichment analysis and GO enrichment analysis were performed with the intersection targets of angina pectoris. The important signaling pathways and biological processes involved in the anti-angina pectoris of Compound Danshen Dropping Pills were predicted. The Surflex-Dock module of SYBYL2.1 software was used for molecular docking of the screened core components and core targets. Results Total 72 active compounds were screened from Compound Danshen Dropping Pills, involving 500 potential targets. The component targets of Compound Danshen Dropping Pills intersected with the targets of angina pectoris, and 457 intersected targets were obtained. The protein-protein interaction (PPI) network of the target of Compound Danshen Dropping Pills in treatment of angina pectoris contains 158 nodes, of which the important targets are STAT3, TP53, AKT1, JUN, MAPK1, HSP90AA1, etc. Compound Danshen Dropping Pills played a role in treatment of angina pectoris by regulating GO biological processes such as inflammatory response, apoptosis signal pathway and actively regulating cell migration, and participating in fluid shear stress and atherosclerosis, PI3K-Akt signal pathway, MAPK signal pathway, HIF-1 signal pathway, TNF signal pathway and IL17 signal pathway. The results of molecular docking showed that the screened active components had strong binding with the target. Conclusion The potential molecular mechanism and target of Compound Danshen Dropping Pills in treatment of angina pectoris were speculated by using the method of network pharmacology. The molecular docking verified that the selected key active ingredients had strong binding activity with important targets.

R285.5

國(guó)家自然科學(xué)基金資助項(xiàng)目（81904038）；陜西省科技廳重點(diǎn)研發(fā)計(jì)劃項(xiàng)目（2020SF-277）；陜西中醫(yī)藥大學(xué)校級(jí)課題（2020GP24）