目的 利用網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接技術(shù)研究槲皮素治療宮腔黏連的潛在作用機(jī)制。方法 在TCMSP數(shù)據(jù)庫查找槲皮素的作用靶點(diǎn)，通過GeneCards、OMIM、DrugBank和PharmGKB數(shù)據(jù)庫，獲取宮腔黏連的相關(guān)靶基因。取兩者交集靶點(diǎn)，利用STRING數(shù)據(jù)庫構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用網(wǎng)絡(luò)，并根據(jù)拓?fù)鋮?shù)分析得到核心靶點(diǎn)。利用Metascape平臺(tái)及微生信平臺(tái)對(duì)核心靶點(diǎn)進(jìn)行基因本體（GO）功能富集分析和京都基因與基因組百科全書（KEGG）通路富集分析，最后利用分子對(duì)接技術(shù)驗(yàn)證槲皮素與核心靶點(diǎn)之間的結(jié)合能力。結(jié)果 槲皮素與宮腔黏連的共同靶點(diǎn)有105個(gè)，其中核心靶點(diǎn)為低氧誘導(dǎo)因子-1α（HIF-1α）、蛋白激酶B1（Akt1）、絲裂原活化蛋白激酶1（MAPK1）、轉(zhuǎn)錄因子AP-1（JUN）等。槲皮素治療宮腔黏連所涉及的主要生物學(xué)過程為對(duì)細(xì)菌源性反應(yīng)、對(duì)脂多糖的反應(yīng)、氧化應(yīng)激及活性氧代謝過程等，關(guān)鍵通路為磷脂酰肌醇-3-激酶（PI3K）/Akt信號(hào)通路、腫瘤壞死因子（TNF）信號(hào)通路、白細(xì)胞介素-17（IL-17）信號(hào)通路等。分子對(duì)接結(jié)果顯示槲皮素與HIF-1α分子對(duì)接效果最好。結(jié)論 槲皮素通過作用于HIF-1α、Akt1、MAPK1等關(guān)鍵靶點(diǎn)，參與PI3K/Akt、TNF、IL-17等信號(hào)通路的調(diào)控，抑制炎癥反應(yīng)及氧化應(yīng)激，從而發(fā)揮治療宮腔黏連的作用。

Objective To study on the mechanism of quercetin in treatment of intrauterine adhesion by using network pharmacology and macromolecular docking. Methods The target of quercetin was found through TCMSP, the target of intrauterine adhesion was obtained through GeneCards, OMIM, DrugBank, and PharmGKB. After taking the intersection target of quercetin and intrauterine adhesion, a protein-protein interaction network was constructed using the STRING database, the core targets were obtianed based on topological parameter analysis. The core targets were used for GO functional enrichment analysis and KEGG pathway enrichment analysis by the Metascape platform and microbiological information platform. Finally, macromolecular docking was used to verify the binding ability between quercetin and the core targets. Results There are 105 common targets of quercetin and uterine adhesion, among which the core targets are HIF-1α, Akt1, MAPK1, JUN, etc. The main biological processes involved in the treatment of uterine adhesion by quercetin include bacterial response, lippolysaccharide response, oxidative stress and reactive oxygen metabolism, etc. The key pathways are PI3K/Akt signaling pathway, TNF signaling pathway, and IL-17 signaling pathway. The results of molecular docking showed that quercetin had the best docking effect with HIF-1α. Conclusion Quercetin acts on HIF-1α, Akt1, MAPK1, and other key targets, participates in the regulation of PI3K/Akt, TNF, IL-17 and other signaling pathways, inhibits inflammatory response and oxidative stress, and thus plays a role in the treatment of uterine adhesions.

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湖南省自然科學(xué)基金項(xiàng)目科衛(wèi)聯(lián)合重點(diǎn)項(xiàng)目（2022JJ70108）；湖南省中醫(yī)藥科研基金一般指導(dǎo)項(xiàng)目（C2023044）；湖南省教育廳重點(diǎn)項(xiàng)目（22A0279）；湖南中醫(yī)藥大學(xué)校級(jí)科研基金項(xiàng)目（C2023044）