基于网络药理学探讨槲皮素治疗结核性溃疡的机制  

Mechanism of quercetin in tuberculous ulcer treatment using network pharmacology

作　　者：郭丹丹[1] 钱佳燕 陈悦 翁嘉晨 黄子慧[1] GUO Dandan;QIAN Jiayan;CHEN Yue;WENG Jiachen;HUANG Zihui(Department of Scrofula,Nanjing Muincipal Hospital of Traditional Chinese and Western Medicine Affiliated to Nanjing University of Traditional Chinese Medicine,Nanjing 210014,China)

机构地区：[1]南京中医药大学附属南京市中西医结合医院瘰疬科,南京210014

出　　处：《中国医科大学学报》2024年第6期509-515,524,共8页Journal of China Medical University

基　　金：江苏省中医药重点科技项目(ZD202105);南京市卫生技术医学重点发展项目(ZKX20049);南京中医药大学自然科学基金(XZR2021086)。

摘　　要：目的基于网络药理学及分子对接方法探讨槲皮素治疗结核性溃疡的分子机制。方法通过PubChem、SwissTarget和TargetNet数据库检索槲皮素的药物靶点,结合课题组前期结核性溃疡基因测序结果,获得交集靶点。利用DAVID数据库完成交集靶点的基因本体(GO)功能富集分析和京都基因和基因组数据库(KEGG)信号通路富集分析。交集靶点经STRING数据库与Cytoscape软件分析其相互作用关系并筛选枢纽节点,采用PyMOL与AutoDock Tolls软件完成槲皮素与枢纽节点的分子对接,筛选以槲皮素为核心的药物靶点,最后构建巨噬细胞模型,对上述核心基因进行验证。结果经筛选共得到54个药物靶点,富集分析结果显示,槲皮素治疗结核性溃疡可涉及的信号通路有代谢通路、脂质与动脉粥样硬化、MAPK信号通路等,另外,ALOX5、TNF、SRC、MMP9、EGFR等基因可能是槲皮素治疗结核性溃疡的关键基因,细胞实验结果表明槲皮素干预后,M1、M2巨噬细胞SRC、EGFR表达水平显著升高,MMP9表达水平显著下降。结论槲皮素可能通过影响SRC、EGFR及MMP9表达发挥其调控巨噬细胞极化的作用。Objective To explore the underlying molecular mechanism of quercetin in tuberculous ulcer treatment using network pharmacology and molecular docking.Methods We identified quercetin drug targets by searching the PubChem,SwissTarget,and TargetNet databases,then combining our results with those of previous tuberculosis ulcer gene sequencing in our group,thereby obtaining intersection targets.Using the DAVID database,we performed intersection target gene ontology functional enrichment analysis and signaling pathway enrichment analysis of the Kyoto gene and genome database.We analyzed the intersection target using the STRING database and Cytoscape software and screened the hub node.We used PyMOL and AutoDockTolls software to complete quercetin molecular docking with the hub node,then screened the core drug target of quercetin.Finally,we constructed a macrophage model to verify the above-mentioned core genes.Results We screened overall 54 drug targets.Our enrichment analysis indicated that the signaling pathways involved in quercetin-mediated tuberculous ulcer treatment were e.g.,metabolic pathways,lipid and atherosclerosis,or the MAPK signaling pathway.In addition,ALOX5,TNF,SRC,MMP9,and EGFR might be the key genes in quercetin-mediated tuberculous ulcer treatment.Results of our cell culture experiment demonstrated that upon quercetin intervention,SRC and EGFR expression increased significantly while that of MMP9 decreased significantly in M1 and M2 macrophages.Conclusion Quercetin could potentially regulate macrophage polarization by influencing SRC,EGFR,and MMP9 expression.

关 键 词：复方五凤草液 槲皮素 结核性溃疡 网络药理学 分子对接技术 

分 类 号：R263[医药卫生—中医外科学]