目的 利用网络药理学和分子对接技术研究槲皮素治疗宫腔黏连的潜在作用机制。方法 在TCMSP数据库查找槲皮素的作用靶点，通过GeneCards、OMIM、DrugBank和PharmGKB数据库，获取宫腔黏连的相关靶基因。取两者交集靶点，利用STRING数据库构建蛋白质-蛋白质相互作用网络，并根据拓扑参数分析得到核心靶点。利用Metascape平台及微生信平台对核心靶点进行基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析，最后利用分子对接技术验证槲皮素与核心靶点之间的结合能力。结果 槲皮素与宫腔黏连的共同靶点有105个，其中核心靶点为低氧诱导因子-1α（HIF-1α）、蛋白激酶B1（Akt1）、丝裂原活化蛋白激酶1（MAPK1）、转录因子AP-1（JUN）等。槲皮素治疗宫腔黏连所涉及的主要生物学过程为对细菌源性反应、对脂多糖的反应、氧化应激及活性氧代谢过程等，关键通路为磷脂酰肌醇-3-激酶（PI3K）/Akt信号通路、肿瘤坏死因子（TNF）信号通路、白细胞介素-17（IL-17）信号通路等。分子对接结果显示槲皮素与HIF-1α分子对接效果最好。结论 槲皮素通过作用于HIF-1α、Akt1、MAPK1等关键靶点，参与PI3K/Akt、TNF、IL-17等信号通路的调控，抑制炎症反应及氧化应激，从而发挥治疗宫腔黏连的作用。

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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湖南省自然科学基金项目科卫联合重点项目（2022JJ70108）；湖南省中医药科研基金一般指导项目（C2023044）；湖南省教育厅重点项目（22A0279）；湖南中医药大学校级科研基金项目（C2023044）