基于网络药理学研究当归-白芍治疗肾病综合征的作用机制  

Study on the mechanism of Danggui and Baishao in the treatment of nephrotic syndrome based on network pharmacology

作　　者：代丽娟 苑伯菲[2] 汪新尧 裴春鹏 陈瑞艳[2] 张佩青[1] DAI Lijuan;YUAN Bofei;WANG Xinyao;PEI Chunpeng;CHEN Ruiyan;ZHANG Peiqing

机构地区：[1]黑龙江省中医药科学院,黑龙江哈尔滨150036 [2]黑龙江中医药大学附属第一医院,黑龙江哈尔滨150040 [3]黑龙江中医药大学,黑龙江哈尔滨150040

出　　处：《中医临床研究》2024年第18期50-55,共6页Clinical Journal Of Chinese Medicine

基　　金：黑龙江省中医药管理局科研项目(ZHY2020-127);黑龙江省博士后面上资助项目(LBH-Z20095);宋立群全国名老中医药专家传承工作室建设项目(国中医药人教函〔2022〕75号);第七批全国老中医药专家学术经验继承工作继承人项目(国中医药人教函〔2022〕76号)。

摘　　要：目的:运用网络药理学方法和分子对接技术探讨当归-白芍治疗肾病综合征的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)数据库挖掘当归-白芍的主要活性成分,通过Pubchem数据库和Swiss Target Prediction数据库进行预测并筛选出当归-白芍活性成分的潜在靶点。将“Nephrotic syndrome”作为关键词输入Disgenet、Genecards和Drugbank数据库进行检索,获取疾病作用靶点。使用Cytoscape软件和STRING数据库,构筑“药物-成分-疾病-靶点”网络图和蛋白相互作用网络,用R软件对关键靶基因进行基因本体论(GO)生物过程富集与京都基因与基因组百科全书(KEGG)信号通路富集分析,并绘制关键靶基因GO及KEGG条形图及气泡图,最后使用分子对接技术将活性成分和靶点进行对接验证。结果:筛选得到当归-白芍有效活性成分15个,涉及作用靶点360个,通过疾病靶点(肾病综合征)与药物靶点(当归-白芍)的重叠,获得与疾病靶点有关的潜在靶点为137个。当归-白芍主要涉及氧化应激过程、炎症反应等生物过程,通过调节磷脂酰肌醇3激酶-蛋白激酶B(Phosphatidylinositol 3-kinase-Akt,PI3K/Akt)、缺氧诱导因子(Hypoxia Inducible Factor,HIF)-1、程序性死亡受体1(Programmed Cell Death Protein 1,PD-1)/程序性死亡配体1(Programmed Deathligand-1,PD-L1)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)、Janus激酶2(Janus Kinase 2,JAK2)/信号转导及转录激活蛋白(Signal Transducer and Activator of Transcription,STAT)3等信号通路来发挥治疗肾病综合征的作用。分子对接结果证实阿魏酸、山柰酚与基质金属蛋白酶(Matrix Metallopeptidase,MMP)9、Toll样受体(Toll-like Receptor,TLR)4、STAT3具有较好的结合活性。结论:当归-白芍治疗肾病综合征的机制可能是通过抑制肾脏炎症反应及氧化应激反应,调节PI3K/Akt、HIF-1、PD-1/PD-L1、MAPK、JAK2/STAT3等信号通路的多途径、多信�Objective:To explore the mechanism of Danggui(angelica root)and Baishao(radix Paeoniae alba)in the treatment of nephrotic syndrome by network pharmacology and molecular docking.Methods:The main active ingredients of angelica-paeonia lactifloria were extracted through TCMSP database and literature,and the potential targets of active ingredients of angelica-Paeonia lactifloria were predicted and screened using Swiss Target Prediction database.According to the database of Disgenet,Genecards and Drugbank,the target of disease is established.CytoScape software and STRING database were used to construct the“drug-component-disease-target-target”network diagram and protein interaction network,And R software was used to perform GO and KEGG functional enrichment analysis of key target genes,and finally molecular docking technology was used to perform docking verification of active components and targets.Results:15 components of Angelica sinensis and paeonia lactiflora paeonia were screened,involving 360 targets and 137 potential targets related to disease targets.Angelica sinensis root is mainly involved in biological processes such as oxidative stress and inflammatory response,and plays a role in the treatment of nephrotic syndrome by regulating the signaling pathways such as PI3K/Akt,HIF-1,PD-1/PD-L1,MAPK and JAK2/STAT3.The results of molecular docking confirmed that ferulic acid and kaophenol had good binding activity with MMP9,TLR4 and STAT3.Conclusion:Angelica sinensis radix paeoniae alba may play a role in the treatment of nephrotic syndrome by inhibiting renal inflammatory response and oxidative stress,regulating multiple pathways and signaling pathways such as PI3K/Akt,HIF-1,PD-1/PD-L1,MAPK,JAK2/STAT3,etc.

关 键 词：网络药理学 肾病综合征 作用机制 

分 类 号：R692[医药卫生—泌尿科学]