目的 運(yùn)用網(wǎng)絡(luò)藥理學(xué)方法和分子對接方法研究京尼平苷治療腦缺血潛在作用機(jī)制。方法 通過PubChem、PharmMapper、GeneCards、OMIM數(shù)據(jù)庫分別對京尼平苷和疾病的靶點(diǎn)進(jìn)行預(yù)測，借助Venny 2.1.0工具將二者取交集獲取共有靶點(diǎn)，通過STRING數(shù)據(jù)庫構(gòu)建交集靶點(diǎn)的蛋白相互作用（PPI）網(wǎng)絡(luò)，隨后通過Cytoscape 3.7.2軟件對核心靶點(diǎn)進(jìn)行網(wǎng)絡(luò)拓?fù)浞治觯换诤诵陌悬c(diǎn)基因開展基因本體（GO）和京都基因與基因組百科全書（KEGG）基因富集分析。利用AutodockTool軟件對所篩選的核心靶點(diǎn)分別與京尼平苷進(jìn)行分子對接。結(jié)果 通過STRING數(shù)據(jù)庫構(gòu)建交集靶點(diǎn)的PPI網(wǎng)絡(luò)，獲得173個(gè)交集靶點(diǎn)，包括酪氨酸蛋白激酶（SRC）、蛋白激酶B1（AKT1）、熱休克蛋白90α家族A級成員1（HSP90AA1）、PIK3R1、表皮生長因子受體（EGFR）等。京尼平苷治療腦缺血可能通過調(diào)控磷脂酰肌醇-3-羥激酶（PI3K）–蛋白激酶B（Akt）信號通路、糖尿病并發(fā)癥中的晚期糖基化終末化產(chǎn)物（AGE）–晚期糖基化終末產(chǎn)物受體（RAGE）信號通路、流體剪切應(yīng)力與動脈粥樣硬化通路、Ras信號通路等多種信號通路發(fā)揮治療腦缺血的作用。結(jié)論 預(yù)測了京尼平苷治療腦缺血的潛在作用機(jī)制，為后續(xù)實(shí)驗(yàn)研究提供理論依據(jù)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.

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浙江省基礎(chǔ)公益研究計(jì)劃（LQ21H090002）；湖北省教育廳科研項(xiàng)目（D20222802）