目的 基于网络药理学的策略来探究抗血小板药物治疗急性肺损伤的机制.方法 通过SwissTargetPrediction平台预测抗血小板药物的靶点,用GeneCards和OMIM数据库获取急性肺损伤的相关靶点.通过STRING平台构建蛋白互作网络,用Cytoscape软件中CytoHubba和MCODE插件,筛选出治疗急性肺损伤的核心靶点和高度连接的靶点簇,使用DAVID数据库对核心靶点进行基因本体(GO)、京都基因与基因百科全书(KEGG)基因富集分析,最后利用AutoDockTools软件进行分子对接验证.结果 总共筛选出20个抗血小板药物治疗急性肺损伤的核心靶点,其中度值排名前3位的核心靶点是原癌基因酪氨酸蛋白激酶(SRC),磷脂酰肌醇3-激酶调节亚基1(PIK3R1)和信号转导与转录激活因子3(STAT3).抗血小板药物可能通过调控表皮生长因子受体(ErbB)信号通路、程序性死亡受体-1(PD-1)/程序性死亡受体配体-1(PD-L1)信号通路、酪氨酸蛋白激酶信号转导与转录激活因子(JAK-STAT)来发挥治疗急性肺损伤的作用,分子对接结果进一步表明,抗血小板药物可以与核心靶点很好地结合.结论 本研究从系统和整体的角度阐明了抗血小板药物治疗急性肺损伤的可能机制,为进一步研究抗血小板药物治疗急性肺损伤的药理机制提供新的思路.
Objective To explore the mechanism of antiplatelet drugs in the treatment of acute lung injury based on the strategy of network pharmacology.Methods The targets of antiplatelet drugs were predicted by SwissTargetPrediction platform,and the related targets of acute lung injury were obtained by GeneCards and OMIM databases.The protein interaction network was constructed through the STRING platform.The CytoHubba and MCODE plug-ins in Cytoscape software were used to screen out the core targets and highly connected target clusters for the treatment of acute lung injury.The DAVID database was used to analyze the gene ontology(GO)bioprocess and Kyoto encyclopedia of genes and genomes(KEGG)signaling pathway enrichment of the core targets.Finally,AutoDockTools software was used for molecular docking verification.Results A total of 20 core targets for antiplatelet drugs in the treatment of acute lung injury were screened,among which the top three core targets were proto-oncogene tyrosine-protein kinase(SRC),phosphoinositide-3-kinase regulatory subunit 1(PIK3R1)and signal transducer and activator of transcription 3(STAT3).Antiplatelet drugs may play a role in the treatment of acute lung injury by regulating epidermal growth factor receptor(ErbB)signaling pathway,positive programmed death receptor-1(PD-1)/programmed death receptor ligand-1(PD-L1)signaling pathway and Janus activated kinase/signal transducer and activator of transcription(JAK-STAT)signaling pathway.Molecular docking results further showed that antiplatelet drugs could bind well to core targets.Conclusion This study elucidated the possible mechanism of antiplatelet drugs in the treatment of acute lung injury from a systematic and holistic perspective,and provided new ideas for further study of the pharmacological mechanism of antiplatelet drugs in the treatment of acute lung injury.
牛镜;向倩;刘志艳;王哲;曹琳玉
徐州医科大学药学院,江苏徐州 221004||北京大学第一医院药学部,北京 100034||北京大学第一医院临床药理研究所,北京 100034北京大学第一医院药学部,北京 100034||北京大学第一医院临床药理研究所,北京 100034
药学
抗血小板药物;网络药理学;急性肺损伤;分子对接
antiplatelet drug;network pharmacology;acute lung injury;molecular docking
《中国临床药理学杂志》 2024 (006)
914-917 / 4
10.13699/j.cnki.1001-6821.2024.06.027
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