基于网络药理学和分子对接探讨补阳还五汤治疗特发性膜性肾病的作用机制  

Exploration on the mechanism of Buyang Huanwu decoction in treating idiopathic membranous nephropathy based on network pharmacology and molecular docking

作　　者：刘兴正 彭玲[1] 杨雪瑞 宋高峰[2] LIU Xingzheng;PENG Ling;YANG Xuerui;SONG Gaofeng

机构地区：[1]广州中医药大学第四临床医学院,广东深圳518033 [2]深圳市中医院,广东深圳518033

出　　处：《中医临床研究》2024年第33期49-54,共6页Clinical Journal Of Chinese Medicine

基　　金：广东省中医药局中医药科研项目(20231300);深圳市中医院2021年度“3030计划”中医临床研究项目(G3030202117)。

摘　　要：目的:探讨补阳还五汤治疗特发性膜性肾病(Idiopathic Membranous Nephropathy,IMN)的活性成分、作用靶点及潜在机制。方法:利用相关数据库查找并筛选补阳还五汤与IMN的相关靶点,运用Cytoscape软件构建“活性成分-共同靶点-疾病”网络图,并筛选核心成分及核心靶点。利用Metascape数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,采用微生信平台进行可视化处理。最后通过Auto Dock软件对核心成分与核心靶点进行分子对接验证。结果:得到补阳还五汤活性成分69个、成分靶点767个、疾病靶点1 703个、成分与疾病交集靶点260个。富集分析涉及2 737个生物过程、169个细胞组分、266个分子功能以及215条相关信号通路。筛选出核心靶点5个,分别为表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)、信号转导和转录激活因子(Signal Transducer and Activator of Transcription,STAT)3、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)3、肿瘤蛋白p53(Tumor Protein p53,TP53)、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1);核心成分3个,为黄芩素、山柰酚、槲皮素。分子对接结果显示核心成分与核心靶点的对接结合能绝大部分都小于–5.0 kcal/mol,表明整体对接结果良好,核心成分与核心靶点之间具有较好的亲和力。结论:补阳还五汤可通过多成分、多靶点、多途径治疗IMN,而其机制可能与通过抑制磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)信号通路、MAPK信号通路发挥抗氧化应激、抑制细胞凋亡、增强自噬等作用有关。Objective:To explore the active ingredients,targets,and potential mechanisms of Buyang Huanwu decoction(补阳还五汤)in the treatment of idiopathic membranous nephropathy.Methods:The relevant targets of Buyang Huanwu decoction and idiopathic membranous nephropathy were searched and screened by relevant database.The‘active ingredients-common targets-disease’network was constructed by Cytoscape software,and core ingredients and core targets were screened.The enrichment analysis of GO and KEGG pathway was carried out by Metascape database,and the visualization process was carried out by Bioinformatics platform.Finally,AutoDock software was used to verify the molecular docking between core ingredients and core targets.Results:A total of 69 active ingredients of Buyang Huanwu decoction,767 ingredient targets,1703 disease targets,and 260 overlapping targets between ingredients and disease were obtained.Enrichment analysis involved 2737 biological processes,169 cellular components,266 molecular functions,and 215 associated signaling pathways.Five core targets were selected,namely,epidermal growth factor receptor(EGFR),signal transducer and transcriptional activator 3(STAT3),mitogen-activated protein kinase 3(MAPK3),tumor protein p53(TP53)and AKT1.There were 3 core components,which were baicalein,kaempferol and quercetin.The results of molecular docking showed that most of the binding energies of core components and core targets were less than-5.0 kcal/mol,indicating that the overall docking results were good,and there was a good affinity between core components and core targets.Conclusion:Buyang Huanwu decoction can treat idiopathic membranous nephropathy through multi-component,multi-target and multi-pathway,and its mechanism may be related to inhibiting PI3K-Akt signaling pathway and MAPK signaling pathway to exert the effects of anti-oxidative stress,inhibition of apoptosis,and enhancement of autophagy.

关 键 词：补阳还五汤 特发性膜性肾病 网络药理学 分子对接 作用机制 

分 类 号：R256.5[医药卫生—中医内科学]