基于网络药理学及分子对接探究大黄-三七-蒲黄治疗脑出血的作用机制  

Exploring the Mechanism of Rhubarb-Sedum Aizoon-Pollen in the Treatment of Intracerebral Hemorrhage Based on Network Pharmacology and Molecular Docking

作　　者：苏卓异 曹然[2] 陈星宇 赵德喜[3] SU Zhuoyi;CAO Ran;CHEN Xingyu;ZHAO Dexi(Changchun University of Chinese Medicine,Changchun 130117,Jilin,China)

机构地区：[1]长春中医药大学,长春130117 [2]长春中医药大学附属传统诊疗医院 [3]长春中医药大学附属医院,长春130021

出　　处：《中西医结合心脑血管病杂志》2023年第13期2372-2382,共11页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金项目(No.81774224);吉林省卫生健康科技能力提升项目(No.2021JC070)。

摘　　要：目的:在活血化瘀理论指导下,运用网络药理学及分子对接方法研究大黄-三七-蒲黄治疗ICH的潜在作用机制。方法:通过中药系统药理学分析平台(TCMSP)、UniPort数据库获取大黄-三七-蒲黄活性成分及靶点蛋白,利用GEO数据库获得GSE24265芯片基因表达谱,运用R软件筛选ICH疾病差异基因,并获取药物与ICH交集靶点。运用Cytoscape软件与STRING数据库获得与靶点相关有效成分及蛋白质-蛋白质相互作用(PPI)网络。通过R Cluster Profiler对交集基因进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。使用Cytoscape软件构建“药物有效成分-靶基因-KEGG网络”,获得药物核心成分及作用靶点。运用GSEA进一步富集核心靶点作用途径。运用Autodock软件分子对接以验证核心成分、靶点的结合活性。结果:筛选获得大黄-三七-蒲黄治疗ICH的核心成分为槲皮素、人参皂苷Rh2、芦荟大黄素等;核心靶点为白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、CXC趋化因子配体8(CXCL8)、趋化因子配体2(CCL2)。核心靶点共同富集于NOD样受体信号通路。分子对接显示,药物核心成分与核心靶点之间具有结合活性。结论:大黄-三七-蒲黄有效成分可通过IL-1β、IL-6、CXCL8、CCL2等靶点,调节NOD样受体信号通路参与调控炎症反应、细胞凋亡等过程,起到对ICH的治疗作用。Objective:Under the guidance of the theory of promoting blood circulation and removing blood stasis,the potential mechanism of rhubarb-Sedum aizoon-Pollen in the treatment of intracerebral hemorrhage(ICH)was studied by network pharmacology and molecular docking method.Methods:The active components and target proteins of rhubarb-Sedum aizoon-Pollen were obtained by Traditional Chinese Medicines Systems Pharmacology Platform(TCMSP)and UniPort database.The gene expression profile of GSE24265 chip was obtained by GEO database.The differential genes of ICH disease were screened by R,and the intersection targets of drugs and ICH were obtained.Cytoscape software and STRING database were used to obtain the target related active components and protein-protein interaction(PPI)network.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of intersecting genes was performed by R Cluster Profiler.Cytoscape software was used to construct the"drug active component-target gene-KEGG network"to obtain the drug core components and targets.GSEA was used to further enrich the core target pathways.Autodock software was used for molecular docking to verify the binding activity of core components and targets.Results:The core components of rhubarb-Sedum aizoon-Pollen for ICH treatment were quercetin,ginsenoside Rh2,aloe emodin,etc.The core targets were interleukin(IL)-1β,IL-6,CXC chemokine ligand 8(CXCL8),and CC chemokine ligand 2(CCL2).The core targets were enriched in NOD like receptor signaling pathway.Molecular docking showed that there was binding activity between drug core components and core targets.Conclusion:The active components of rhubarb-Sedum aizoon-Pollen can regulate NOD-like receptor signaling pathway to participate in the regulation of inflammatory response and apoptosis through IL-1β,IL-6,CXCL8,CCL2,and other targets,and play a therapeutic role in ICH.

关 键 词：脑出血 网络药理学 分子对接 大黄 三七 蒲黄 作用机制 

分 类 号：R285[医药卫生—中药学]