目的 采用網(wǎng)絡(luò)藥理學(xué)和分子對接技術(shù)探討杜仲治療先兆流產(chǎn)的潛在作用靶點(diǎn)及其分子機(jī)制。方法 基于前期的研究成果，結(jié)合中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）和文獻(xiàn)報道補(bǔ)充篩選杜仲的活性成分，從GeneCards、OMIM和DisGeNET數(shù)據(jù)庫中篩選先兆流產(chǎn)疾病靶點(diǎn)，利用韋恩圖繪制平臺獲取共有靶點(diǎn)后，導(dǎo)入Cytoscope3.9.0軟件和STRING在線分析平臺，進(jìn)行網(wǎng)絡(luò)拓?fù)鋵W(xué)分析。通過DAVID數(shù)據(jù)庫對核心靶點(diǎn)進(jìn)行基因本體（GO）功能分析和京都基因與基因組百科全書（KEGG）信號通路富集分析；最后采用AutoDockTools 1.5.6軟件進(jìn)行分子對接驗(yàn)證，并將對接結(jié)果可視化。結(jié)果 共篩選得到包括β-胡蘿卜素、綠刺桐靈、山柰酚、丁香黃素、槲皮素等16個杜仲潛在活性成分，通過預(yù)測得到的成分靶點(diǎn)387個，疾病靶點(diǎn)5 287個，并得到共同靶點(diǎn)247個；經(jīng)蛋白質(zhì)相互作用（PPI）分析及網(wǎng)絡(luò)拓?fù)浞治龊?，獲取核心靶點(diǎn)10個，包括絲氨酸/蘇氨酸蛋白激酶（Akt1）、酪氨酸蛋白激酶轉(zhuǎn)化蛋白（SRC）、半胱氨酸蛋白酶3(CASP3)、表皮生長因子受體（EGFR）、雌激素受體（ESR1）、缺氧誘導(dǎo)因子-1α(HIF-1A)、前列腺素G/H合酶2(PTGS2)、基質(zhì)金屬蛋白酶9(MMP9)、熱休克蛋白HSP90-β(HSP90AB1)、糖原合成酶激酶-3β(GSK3B)。GO富集到基因功能120個，KEGG富集到信號通路53條，分析結(jié)果表明，KEGG富集分析關(guān)鍵靶點(diǎn)主要富集在癌癥通路、癌癥中的蛋白聚糖、雌激素信號通路等信號通路中；分子對接結(jié)果顯示核心成分與核心靶點(diǎn)具有較好的構(gòu)象。結(jié)論 揭示了杜仲在預(yù)防先兆流產(chǎn)中的多成分、多靶點(diǎn)、多通路的作用機(jī)制。

Objective To explore the potential targets and molecular mechanism of Eucommiae Cortex in treatment of threatened abortion by network pharmacology and molecular docking. Methods Based on the research results, combined with the TCMSP, and literature reports, the active components of Eucommiae Cortex were screened. And the targets of threatened abortion were screened from the GeneCards, OMIM, and DisGeNET database. The common targets were obtained by using the Venn diagram drawing platform, and the information was imported into Cytoscope 3.9.0 software and STRING online analysis platform for network topology analysis. GO function analysis and KEGG signal pathway enrichment analysis were performed on the core targets through the DAVID database. Finally, AutoDockTools 1.5.6 software was used for molecular docking verification, and the docking results were visualized.Results A total of 16 potential active components of Eucommiae Cortex were screened, such as β-carotene, erythraline, kaempferol, syringetin, quercetin, and 387 component targets, 5 287 disease targets, and 247 common targets were obtained by prediction. After protein interaction analysis and network topology analysis, 10 core targets were obtained, including Akt1, SRC, CASP3, EGFR, ESR1, HIF-1A, PTGS2, MMP9, HSP90AB1, GSK3B. GO was enriched to 120 gene functions, and KEGG was enriched to 53 signaling pathways. The analysis results showed that the key targets of KEGG enrichment analysis were mainly enriched in cancer pathways, proteoglycans in cancer, estrogen signaling pathways and other signaling pathways. The results of molecular docking showed that the core component and the core target had a good conformation. Conclusion The multi-component, multi-target and multi-pathway mechanism of Eucommiae Cortex in preventing threatened abortion was revealed.

R285.5

浙江省基礎(chǔ)公益研究計劃項(xiàng)目(LTGN23H280001); 浙江省中醫(yī)藥科技計劃中醫(yī)藥現(xiàn)代化專項(xiàng)項(xiàng)目(2020ZX006); 杭州市農(nóng)業(yè)與社會發(fā)展科研重點(diǎn)項(xiàng)目(202204A06)