基于网络药理学探究黄连调控巨噬细胞干预动脉粥样硬化斑块稳定性的潜在机制  

Exploration on the potential mechanism of Coptis chinensis Franch in regulating macrophages to intervene the stability of atherosclerosis plaque based on network pharmacology

作　　者：刘婷 韩慧子 向磊 赵梦涵 俞琦 LIU Ting;HAN Huizi;XIANG Lei;ZHAO Menghan;YU Qi(School of Basic Medicine,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,Guizhou,China)

机构地区：[1]贵州中医药大学基础医学院,贵州贵阳550025

出　　处：《右江医学》2023年第8期678-683,共6页Chinese Youjiang Medical Journal

基　　金：国家自然科学基金(81860776)。

摘　　要：目的探究黄连调控巨噬细胞干预动脉粥样硬化斑块稳定性的潜在机制。方法对GEO数据库中的动脉斑块相关数据集进行差异分析得到巨噬细胞干预动脉粥样硬化斑块相关基因。从TCMSP数据库获取黄连的有效成分和潜在靶点。对两者取交集后找出发挥作用的化学成分和潜在靶点。对潜在靶点进行蛋白质-蛋白质相互作用(PPI)、基因本体(GO)、京都基因与基因组百科全书(KEGG)分析,探究黄连调控巨噬细胞干预动脉粥样硬化斑块稳定性的作用机制。结果稳定斑块组和破裂斑块组差异分析共找到892个差异基因。通过TCMSP共找出黄连中的11个化学成分,251个靶点。两者取交集后得到16个黄连调控巨噬细胞的潜在靶点。PPI结果显示,DPP4、TNFAIP6、IL6ST、POR、RUNX1T1、HMOX1、CAV1等16个交集基因之间有较强的相互作用关系,且DPP4、HMOX1、CAV1和VCAM1处于PPI网络的枢纽位置。GO结果表明,生物学过程(BP)与对脂多糖的反应、对细菌来源分子的反应、对T细胞激活的正向调节等有关。细胞组成(CC)与膜筏、膜微区、膜区等细胞器有关。分子功能(MF)参与肽酶活化剂活性、趋化因子活性等分子功能的调节。KEGG结果与流体剪切应力及动脉粥样硬化、NF-kappa B信号传导途径有关。结论黄连内槲皮素可能通过调节DPP4、HMOX1、CAV1等靶点影响斑块内巨噬细胞的信号传导途径,进而干预斑块稳定性。Objective To investigate the potential mechanisms of Coptis chinensis Franch in regulating macrophages to intervene the stability of atherosclerosis plaque.Methods Differential analysis of arterial plaque related datasets from GEO database was performed to obtain macrophage intervention in atherosclerotic plaque related genes.The active ingredients and potential targets of Coptis chinensis Franch were obtained from TCMSP database,and the intersection of the two was taken to identify the chemotactic components and potential targets that play a role.Protein-protein interactions(PPI),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the potential targets to investigate the mechanism of action of Coptis chinensis Franch in regulating macrophages to intervene the stability of atherosclerosis plaque.Results A total of 892 differential genes were found in the differential analysis of the stable and ruptured plaque groups.11 chemical components and 251 targets in Coptis chinensis Franch were identified by TCMSP,and 16 potential targets of Coptis chinensis Franch were obtained after taking the intersection of the two.PPI results showed that there were strong interactions between 16 intersecting genes,including DPP4,TNFAIP6,IL6ST,POR,RUNX1T1,HMOX1 and CAV1,etc.And DPP4,HMOX1,CAV1 and VCAM1 were at the pivotal position of the PPI network.GO results showed that biological process(BP)was associated with response to lipopolysaccharide,response to molecules of bacterial origin,and positive regulation of T cell activation.Cell composition(CC)was associated with organelles such as membrane rafts,membrane microregions,and membrane zones.Molecular function(MF)was involved in the regulation of molecular functions such as peptidase activator activity and chemokine activity.KEGG results were related to fluid shear stress and signal transduction of atherosclerosis and NF-kappa B signal transduction pathway.Conclusion Quercetin within Coptis chinensis Franch may affect the intraplaque macrophage s

关 键 词：黄连 巨噬细胞 动脉粥样硬化 斑块稳定性 网络药理学 

分 类 号：R543.5[医药卫生—心血管疾病]