基于网络药理学和分子对接研究越鞠丸治疗股骨头坏死和慢性疼痛伴抑郁症的作用机制  

Study on the mechanism of action of treating osteonecrosis of femoral head and chronic pain with depression with Yueju Wan based on network pharmacology and molecular docking

作　　者：黎登宸 梅凌 黄文茁 董晓俊 LI Dengchen

机构地区：[1]湖北中医药大学,湖北武汉430065 [2]湖北中医药大学附属国医医院/武汉市中医医院,湖北武汉430014

出　　处：《中医临床研究》2023年第31期9-18,共10页Clinical Journal Of Chinese Medicine

摘　　要：目的:通过分析越鞠丸的有效成分,研究其治疗股骨头坏死和慢性疼痛伴抑郁症异病同治的作用机制。方法:借助中药系统药理学数据库与分析平台(TCMSP)检索越鞠丸的化学成分和作用靶点,采用Uniprot查询与靶点对应的基因,应用GeneCards数据库查询与股骨头坏死及慢性疼痛伴抑郁症两种疾病相关的基因。将越鞠丸4味中药关键成分的靶点信息分别和股骨头坏死以及慢性疼痛伴抑郁症的靶点基因进行相互映射,进而运用CytoScape 3.9.1分别构建两疾病的化合物-靶点(基因)网络、蛋白质-蛋白质相互作用网络,筛选出两者的核心靶点。通过DAVID进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。最后进行靶点-通路网络构建以及分子对接分析,研究越鞠丸对两者的作用机制。结果:越鞠丸的4种关键化合物(槲皮素、山柰酚、豆甾醇、β-谷甾醇)均同时作用于股骨头坏死和慢性疼痛伴抑郁症的靶点基因,两疾病共有的核心基因为白细胞介素(Interleukin,IL)-6、IL-1B、肿瘤抑制蛋白p53(Tumor Protein p53,TP53)、基质金属蛋白酶(Matrix Metallopeptidase 9,MMP9),GO富集结果显示生物过程-基因表达的正向调节、分子功能-酶结合、细胞组分-细胞外空间和细胞外区域为两种疾病共有部分,KEGG通路分析后取交集发现晚期糖基化终末产物(Advanced Glycation End-product,AGE)与其受体(Receptor for Advanced Glycation End Products,RAGE)信号通路、脂质和动脉粥样硬化通路、流体剪切应力和动脉粥样硬化通路以及癌症通路是两种疾病共通的信号通路;分子对接结果显示,槲皮素、山柰酚与MMP9结合最优,豆甾醇、β-谷甾醇与TP53-结合蛋白1结合最优。结论:越鞠丸以多种活性成分、多个作用靶点和途径发挥其异病同治股骨头坏死和慢性疼痛伴抑郁症的作用,为越鞠丸的临证运用提供理论依据。Objective:To study the mechanism of action of Yueju Wan(越鞠丸)in the treatment of osteonecrosis of the femoral head and chronic pain with depression by analyzing the active ingredients of Yueju Wan.Methods:The chemical constituents and action targets of Yueju Wan were searched by TCMSP,the genes corresponding to the targets were searched by Uniprot,and the genes related to osteonecrosis of the femoral head and chronic pain with depression were searched by GeneCards database.The target information of the four key components of Yueju Wan was mapped with the target genes of osteonecrosis of the femoral head and chronic pain with depression respectively.Then the compound-target(gene)network and protein-protein interaction network of the two diseases were constructed by CytoScape 3.9.1,and the core targets of the two diseases were screened.GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out by DAVID.Finally,the target-pathway network construction and molecular docking analysis were carried out to study the action mechanism of Yueju Wan on both.Results:Four key compounds of Yueju Wan(quercetin,kaempferol,stigmasterol andβ-sitosterol)all acted on the target genes of osteonecrosis of femoral head and chronic pain with depression at the same time.The core genes shared by the two diseases are IL-6,IL-1B,TP53 and MMP9.GO enrichment results showed that biological processpositive regulation of gene expression,molecular function-enzyme binding,cellular component-extracellular space,extracellular region was the common part of the two diseases.After KEGG pathway analysis,intersection found that AGE-RAGE signaling pathway,lipid and atherosclerotic pathway,fluid shear stress and atherosclerotic pathway,and cancer pathway are common signal pathways of the two diseases.The results of molecular docking showed that quercetin and kaempferol had the best binding with MMP9,and stigmasterol andβ-sitosterol had the best binding with TP53-binding protein 1.Conclusion:Yueju Wan plays a role in the tr

关 键 词：越鞠丸 股骨头坏死 慢性疼痛伴抑郁症 网络药理学 异病同治 

分 类 号：R284.6[医药卫生—中药学]