通过综合网络信息方法深入了解EPA治疗ANCA相关血管炎的分子机制  

Insights into the biological targets and molecular mechanisms of EPA for the treatment of AAV through an integrated network information approach

作　　者：夏梦迪[1] 冯胜刚[1] 谢席胜[1] 蒲廷 XIA Mengdi;FENG Shenggang;XIE Xisheng;PU Ting(Department of Nephrology,Nanchong Central Hospital,Nanchong Key Laboratory of Basic Science&Clinical Research on Chronic Kidney Disease,Nanchong 637000,Sichuan,China;Sichuan Cancer Hospital,University of Electronic Science and Technology School of Medicine Mega Data Center,Chengdu 610041,China)

机构地区：[1]川北医学院附属南充市中心医院肾内科•南充市慢性肾脏病基础科学与临床研究重点实验室,四川南充637000 [2]四川省肿瘤医院•电子科技大学医学院大数据中心,四川成都610041

出　　处：《西部医学》2023年第5期679-686,共8页Medical Journal of West China

基　　金：四川省中医药管理局项目(2020LC01446);南充市市校科技战略合作专项(20SXQT0117)。

摘　　要：目的通过网络药理学和分子对接的研究方法预测二十碳五烯酸(EPA)辅助治疗ANCA相关性血管炎(AAV)的分子作用机制。方法通过PubChem获取EPA的三维结构和相应的结构式,在STITCH、Swiss Target Prediction、Pharmmapper和CTD数据库获取药效团预测靶点,并将获取药效团预测靶点并与GeneCards、OMIM和Disgenet数据库获取的AAV疾病靶点做交集,得到关键靶点,运用STRING数据库和Cytoscape软件构建蛋白互作网络;对有效靶点进行GO分析及KEGG相关通路的富集分析;通过Autodock对成分靶点进行分子对接验证。结果获得116个EPA治疗AAV潜在作用靶点,关键靶点包括TNF,IL6,ALB,TP53,IL1β,MAPK3,CASP3,PTGS2,PPARG,CCL2等。GO富集分析有1503个GO术语(P<0.05),KEGG中有1503个信号通路(P<0.05)主要富集在癌症、脂质和动脉硬化、TNF信号传导途径、神经变性的途径——多种疾病和IL-17信号传导途径等多个信号通路。分子对接结果发现EPA与免疫炎症、细胞凋亡及脂质代谢相关目标靶点能很好结合。结论本研究初步揭示了EPA治疗AAV的潜在靶点、涉及的生物过程及信号通路,为进一步研究奠定了基础。Objective This study aimed to clarify the molecular mechanism of action of Eicosapentaenoic acid(EPA)on the treatment of Antineutrophil Cytoplasmic antibody-associated Vasculitis(AAV)via network pharmacology and molecular docking.Methods The three-dimensional structure and corresponding structural formula of EPA were obtained by PubChem.Potential therapeutic targets of AAV were collected using the GeneCards,OMIM,Disgenet,and CTD databases.The predicted pharmacodynamic targets were obtained by STRING database and Cytoscape software and intersected with the obtained AAV disease targets to obtain the intersection targets.Then,we established protein-protein interaction(PPI).Metascape database was utilized for GO and KEGG pathway analysis.Molecular docking techniques were used to estimate the binding force between the EPA and the hub genes.Results There were 116 potential targets of EPA for the treatment of AAV were obtained.PPI analysis showed that IL6,ALB,TP53,IL1β,MAPK3,CASP3,PTGS2,PPARG,and CCL2 shared the highest centrality among all target genes.GO enrichment analysis showed 1503 GO terms enriched.KEGG pathway analysis showed 1503 signaling pathways mainly enriched and found that cancer,lipid and atherosclerosis,TNF signaling pathway,pathways of neurodegeneration-multiple diseases and IL-17 signaling pathway may occupy core status.Molecular docking results showed that the EPA had a strong binding affinity to the immune inflammation,apoptosis,and lipid metabolism related hub genes.Conclusion Verified by a network pharmacology approach based on data mining and molecular docking methods,EPA may serve as a promising adjuvant therapeutic candidate for AAV,which laid the foundation for further basic and clinic research.

关 键 词：二十碳五烯酸 血管炎 网络药理学 分子对接 

分 类 号：R593.2[医药卫生—内科学]