目的 运用网络药理学方法和分子对接方法研究京尼平苷治疗脑缺血潜在作用机制。方法 通过PubChem、PharmMapper、GeneCards、OMIM数据库分别对京尼平苷和疾病的靶点进行预测，借助Venny 2.1.0工具将二者取交集获取共有靶点，通过STRING数据库构建交集靶点的蛋白相互作用（PPI）网络，随后通过Cytoscape 3.7.2软件对核心靶点进行网络拓扑分析；基于核心靶点基因开展基因本体（GO）和京都基因与基因组百科全书（KEGG）基因富集分析。利用AutodockTool软件对所筛选的核心靶点分别与京尼平苷进行分子对接。结果 通过STRING数据库构建交集靶点的PPI网络，获得173个交集靶点，包括酪氨酸蛋白激酶（SRC）、蛋白激酶B1（AKT1）、热休克蛋白90α家族A级成员1（HSP90AA1）、PIK3R1、表皮生长因子受体（EGFR）等。京尼平苷治疗脑缺血可能通过调控磷脂酰肌醇-3-羟激酶（PI3K）–蛋白激酶B（Akt）信号通路、糖尿病并发症中的晚期糖基化终末化产物（AGE）–晚期糖基化终末产物受体（RAGE）信号通路、流体剪切应力与动脉粥样硬化通路、Ras信号通路等多种信号通路发挥治疗脑缺血的作用。结论 预测了京尼平苷治疗脑缺血的潜在作用机制，为后续实验研究提供理论依据和研究方向。

Objective To study the potential mechanism of geniposide in treatment of cerebral ischemia by network pharmacology and molecular docking. Methods PubChem, PharmMapper, GeneCards, and OMIM databases were used to predict the targets of geniposide and disease respectively. Venny 2.1.0 tool was used to obtain the intersection of the two targets, and the protein interaction network of the intersection targets was constructed through STRING database. Cytoscape 3.7.2 software was used to analyze the network topology of the core target. GO and KEGG gene enrichment analysis was carried out based on the core target genes. AutodockTool software was used to dock the selected core targets with geniposide. Results The protein interaction network of intersection targets was constructed by STRING database, and 173 intersection targets were obtained, including SRC, AKT1, HSP90AA1, PIK3R1, EGFR, etc. Geniposide may regulate PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis pathway, Ras in treatment of cerebral ischemia signaling pathway and other signaling pathways play a role in the treatment of cerebral ischemia. Conclusion This study predicts the potential mechanism of geniposide in the treatment of cerebral ischemia, and provides theoretical basis and research direction for subsequent experimental research.

R285

浙江省基础公益研究计划（LQ21H090002）；湖北省教育厅科研项目（D20222802）