基于网络药理学和分子对接探讨三妙丸治疗糖尿病足溃疡的作用机制  

Exploration on the mechanism of Sanmiao Wan in the treatment of diabetic foot ulcer based on network pharmacology and molecular docking

作　　者：张筱茜 范琦琛 王艮一 王雁南[2] ZHANG Xiaoqian

机构地区：[1]山东中医药大学,山东济南250014 [2]山东中医药大学附属医院,山东济南250014

出　　处：《中医临床研究》2023年第26期98-103,共6页Clinical Journal Of Chinese Medicine

基　　金：山东省中医药科技发展计划项目基金资助(2019-0202);齐鲁医派中医学术流派传承项目基金资助(鲁卫函[2022]93号);全国名老中医药专家传承工作室建设项目基金资助(国中医药人教函[2022]75号)。

摘　　要：目的:应用网络药理学和分子对接技术研究三妙丸治疗糖尿病足溃疡的作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)筛选三妙丸的有效成分及作用靶点,在多个数据库中联合挖掘糖尿病足溃疡的治疗靶点,获得三妙丸-糖尿病足溃疡共有靶点,构建中药调控及蛋白质-蛋白质相互作用网络。筛选出核心基因,再进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,找出所涉及的信号通路,最后利用AutoDock Tools、Vina及Pymol对有效成分与核心靶点进行分子对接。结果:获得三妙丸中主要有效成分50个,潜在作用靶点677个,涉及糖尿病足溃疡靶点711个、两者共同靶点86个。其中有效成分包括槲皮素、汉黄芩素、β-艾蒿素及β-谷甾醇等,核心靶点包括缺氧诱导因子(Hypoxia Inducible Factor,HIF)1A、血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF)A、信号转导与转录激活因子(Signal Transducer and Activator of Transcription,STAT)1等。GO富集分析得到生物过程条目2067个、细胞成分条目48个、分子功能条目144个。KEGG通路富集分析得到160条信号通路,主要涉及晚期糖基化终末产物(Advanced Glycation End Products,AGE)-AGE受体(Receptor for AGE,RAGE)信号通路、磷酯酰肌醇3激酶(Phosphatidylinositol 3 Kinase,PI3K)/蛋白激酶B(Akt)信号通路、肿瘤坏死因子(Tumor Necrosis Factor,TNF)信号通路等。分子对接结果显示,三妙丸关键有效成分与糖尿病足溃疡核心靶点可自由结合。结论:三妙丸可能主要通过槲皮素、汉黄芩素、β-艾蒿素及β-谷甾醇等有效成分调节HIF1A、VEGFA、STAT1等靶点,进而影响多条信号通路,通过调节炎症反应与氧化应激反应等治疗糖尿病足溃疡。Objective:To explore the action mechanism of Sanmiao Wan(三妙丸)in the treatment of diabetic foot ulcer(DFU)based on network pharmacology and molecular docking technology.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was used to screen the active ingredients and target genes of Sanmiao Wan,the DFU-related target genes were retrieved in databases.Sanmiao Wan and DFU target genes were mapped to obtain common target genes.PPI network was constructed,the core genes were screened out,and then GO enrichment analysis and KEGG pathway enrichment analysis were carried out to find out the signal pathways involved.Finally,AutoDock Tools,Vina and Pymol were used to conduct molecular docking between the active ingredient and the core genes.Results:There were 50 main active ingredients including quercetin,wogonin,β-vulgarin andβ-sitosterol in Sanmiao Wan,with 677 target genes.There were 711 target genes for DFU,and 86 common target genes.The core genes included HIF1A,VEGFA,STAT1,etc..GO enrichment analysis revealed 2067 biological processes,48 cellular components and 144 molecular functions.KEGG pathway enrichment analysis obtained 160 signaling pathways,mainly involving AGE-RAGE signaling pathway,PI3K/Akt signaling pathway,TNF signaling pathway,and other signaling pathways.Molecular docking results showed that the key active ingredients of Sanmiao Wan could be freely combined with the core genes of DFU.Conclusion:Sanmiao Wan may mainly regulate HIF1A,VEGFA,STAT1 and other target genes through active ingredients such as quercetin,wogoninβ-vulgarin andβ-sitosterol,thereby affecting multiple signaling pathways and regulating inflammatory response and oxidative stress response in the treatment of DFU.

关 键 词：三妙丸 糖尿病足溃疡 网络药理学 分子对接 作用机制 

分 类 号：R256[医药卫生—中医内科学]