目的 利用網(wǎng)絡藥理學和分子對接的方法探討苗藥土大黃防治功能性子宮出血（DUB）的潛在作用機制。方法 基于文獻研究篩選得到土大黃主要活性成分，利用Swiss Target Prediction平臺預測土大黃的作用靶點，利用OMIM、DrugBank、DisGeNet、GeneCards數(shù)據(jù)庫確定DUB的疾病靶點，并通過Venny 2.1.0在線工具將其與土大黃靶點取交集后獲得土大黃防治DUB的潛在作用靶點；在STRING數(shù)據(jù)庫進行蛋白互作網(wǎng)（PPI）分析，結(jié)合Cytoscape 3.8.2 軟件篩選關(guān)鍵靶點。將篩選得到的交集靶點導入DAVID數(shù)據(jù)庫進行基因本體（GO）和京都基因與基因組百科全書（KEGG）富集分析。最后運用AutoDock Tools軟件將篩選出的關(guān)鍵成分與關(guān)鍵靶點進行分子對接驗證。結(jié)果 結(jié)合文獻研究與Swiss Target Prediction平臺篩選得到藥物活性成分26個，藥物靶點392個，疾病靶點436個，共同靶點74個；經(jīng)PPI及網(wǎng)絡拓撲分析后，獲取核心靶點7個，分別是信號轉(zhuǎn)導和轉(zhuǎn)錄激活因子3（STAT3）、原癌基因酪氨酸蛋白激酶（SRC）、磷酸肌醇3-激酶調(diào)節(jié)亞基1（PIK3R1）、磷脂酰肌醇3-激酶催化亞基α（PIK3CA）、雌激素受體（ESR1）、絲氨酸/蘇氨酸蛋白激酶1（AKT1）、轉(zhuǎn)錄因子p65（RELA）；經(jīng)活性成分–核心靶點網(wǎng)絡的構(gòu)建及網(wǎng)絡拓撲分析，得到土大黃防治DUB主要活性成分9個，分別是槲皮素、阿魏酸、豆蔻酸、羥基大黃素、決明柯酮、大黃素甲醚、委陵菜酸、大黃酚、3,4-二羥基苯甲酸乙酯；GO富集到基因功能303個（P＜0.01），KEGG富集到基因通路122條（P＜0.01），結(jié)果表明，土大黃防治DUB的作用機制是通過調(diào)節(jié)低氧誘導因子-1（HIF-1）、磷酸化磷脂酰肌醇-3-激酶（p-PI3K）–蛋白激酶B（Akt）等信號通路來發(fā)揮防治DUB的作用。分子對接驗證結(jié)果顯示，關(guān)鍵活性成分與核心靶點均可自發(fā)結(jié)合。結(jié)論 初步揭示了土大黃防治DUB的有效成分和可能的作用機制，并為深入研究藥效物質(zhì)基礎(chǔ)、作用機制以及臨床應用提供了科學參考。

Objective To explore the potential mechanism of Rumei Radix et Rhizoma in prevention of functional uterine bleeding(DUB) by network pharmacology and molecular docking methods. Methods The main active components of Rumei Radix et Rhizoma were screened based on literature study. The Swiss Target Prediction platform was used to predict the target of DUB, and the disease target was determined by OMIM, DrugBank, DisGeNet and GeneCards databases. The potential target of DUB control of Rumei Radix et Rhizoma was obtained by intersection of DUB target and Rumei Radix et Rhizoma target through Venny 2.1.0 online tool. Protein interaction network (PPI) analysis was performed on STRING database, combined with Cytoscape 3.8.2 software to screen key targets. The selected intersection targets were imported into DAVID database for GO biological function and KEGG enrichment analysis. Finally, AutoDock Tools software was used to verify the molecular docking between the selected key components and key targets. Results Based on literature study and Swiss Target Prediction platform, 26 drug active ingredients, 392 drug targets, 436 disease targets, and 74 common targets were identified. After protein interaction analysis (PPI) and network topology analysis, 7 core targets were obtained, which were STAT3, SRC, PIK3R1, PIK3CA, ESR1, AKT1, and RELA. Through the construction of the active ingredient-core target network and network topology analysis, 9 main active ingredients of Rumei Radix et Rhizoma control DUB were obtained. They are quercetin, ferulic acid, myrianthic acid, citreorosein, torachrysone, physcion, tormentic acid, chrysophanol, ethyl 3,4-dihydroxybenzoate; GO enriched 303 gene functions (P < 0.01), KEGG enriched 122 gene pathways (P < 0.01). The results showed that the mechanism of DUB prevention and control was through the regulation of HIF-1, PI3K-Akt and other signaling pathways. The results of molecular docking showed that both the key active ingredient and the core target could spontaneously bind. Conclusion This study preliminarily revealed the effective components and possible mechanism of action of Rumei Radix et Rhizoma in the prevention and treatment of DUB, and provided scientific reference for further study on the basis of effective substances, mechanism of action and clinical application.

R285.5；R984

貴州省教育廳自然科學研究項目（黔教合KY字[2021]203）