基于生物信息学分析和网络药理学探讨黄连解毒汤干预动脉粥样硬化斑块破裂的作用机制  

Based on bioinformatics analysis and network pharmacology to explore mechanism of Huanglian Jiedu Decoction in intervention of atherosclerotic plaque rupture

作　　者：李晓辉 彭广操[1] 李兴渊[1] 王建茹(指导) LI Xiaohui;PENG Guangcao;LI Xingyuan;WANG Jianru(The First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学第一附属医院,郑州450000

出　　处：《中国免疫学杂志》2022年第14期1702-1710,共9页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(82004311)。

摘　　要：目的:基于生物信息学分析和网络药理学探讨黄连解毒汤(HLJDD)延缓或抑制动脉粥样硬化(AS)由稳定斑块到破裂过程的作用机制。方法:从GEO和ArrayExpress数据库中获取含有人颈AS稳定和破裂斑块的数据集;利用limma包和wilcoxTest筛选差异表达基因(DEGs),再用稳健排序整合(RRA)方法筛选稳健DEGs,并进行富集分析。利用TCMSP和Swiss Target Prediction数据库筛选HLJDD的活性成分及其作用靶点,并与稳健DEGs取交集,获取HLJDD-AS交集DEGs。对交集DEGs进行功能富集分析,并构建蛋白互作(PPI)网络,筛选PPI网络中的子模块和Hub基因。利用Autodock Vina软件将Hub基因与其所对应HLJDD的活性成分进行分子对接。结果:RRA法共鉴定出864个稳健DEGs,其功能主要涉及中性粒细胞的脱颗粒、活化、炎症反应、趋化因子信号通路、PPAR信号通路、细胞黏附分子等。筛选出HLJDD有84个活性成分、928个作用靶点,获得HLJDD-AS交集DEGs有42个。GO和KEGG分析显示,交集DEGs主要涉及胶原蛋白的分解代谢、组织重构、中性粒细胞的脱颗粒、活化、PPAR信号通路、补体与凝血级联反应等。在PPI网络中,共筛选2个子模块,7个Hub基因。分子对接结果显示,7个Hub基因与其对应HLJDD的活性成分表现出了良好的亲和力。结论:本研究揭示了以清热解毒为治则的HLJDD有效抑制或延缓AS斑块破裂的作用机制,为中医从毒论治AS易损斑块提供一定的科学依据。Objective:To explore the mechanism of Huanglian Jiedu Decoction(HLJDD)in delaying or inhibiting the process of atherosclerosis(AS)from stable plaque to rupture based on bioinformatics analysis and network pharmacology.Methods:Data sets containing stable and ruptured human AS plaques were obtained from GEO and ArrayExpress databases. Differentially expressed genes(DEGs)were screened by limma package and wilcoxTest,and robust rank aggregation(RRA)method was used to screen robust DEGs,and enrichment analysis was performed. TCMSP and Swiss Target Prediction database were used to screen the active components and targets of HLJDD,and intersected with robust DEGS to obtain the intersection DEGs of HLJDD-AS. The functional enrichment analysis was performed on intersection DEGs,and PPI network was constructed to screen the sub modules and Hub genes in the PPI network. The Autodock Vina software was used to conduct molecular docking between Hub gene and its corresponding active components of HLJDD.Results:A total of 864 robust DEGs were identified by RRA,whose functions were mainly involved in neutrophils degranulation,activation,inflammatory response,chemokine signaling pathway,PPAR signaling pathway,cell adhesion molecules and so on. HLJDD had 84 active ingredients and 928 targets,and 42 HLJDD-AS intersection DEGs were obtained. GO and KEGG analysis showed that the intersecting DEGs mainly involved in collagen catabolism,tissue remodeling,neutrophil degranulation,activation,PPAR signaling pathway,complement and coagulation cascade reaction and so on. In PPI network,a total of 2 submodules and 7 Hub genes were screened. The results of molecular docking showed that the 7 Hub genes showed good affinity with their corresponding active components of HLJDD.Conclusion:This study reveals the mechanism of HLJDD,which uses heat-clearing and detoxification as the treatment principle,to effectively inhibit or delay the rupture of AS plaques,and provides a scientific basis for the treatment of AS vulnerable plaques from the theory of

关 键 词：动脉粥样硬化 黄连解毒汤 清热解毒 生物信息学 网络药理学 

分 类 号：R285[医药卫生—中药学]