基于“血实宜决之”理论运用网络药理学讨论丹参-海风藤治疗紫癜性肾炎的作用机制  

Discussion on the mechanism of Danshen-Haifengteng on henoch-schonlein purpura nephritis based on“Blood-excess syndrome should be treated by removing therapy”theory by network pharmacology

作　　者：李旭峰 白晓红[2] 修婵[2] 杨姝荟 LI Xufeng;BAI Xiaohong;XIU Chan;YANG Zhuhui

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110847

出　　处：《中医临床研究》2023年第33期111-118,共8页Clinical Journal Of Chinese Medicine

摘　　要：目的:基于“血实宜决之”理论运用网络药理学讨论丹参-海风藤治疗紫癜性肾炎(Henoch-Schonlein Purpura Nephritis,HSPN)的作用机制。方法:“血实宜决之”出自《素问•阴阳应象大论篇》,是活血化瘀法的治疗总纲。基于“血实宜决之”理论,选取“丹参-海风藤”作为研究药物。使用中药系统药理学数据库与分析平台(TCMSP)获取丹参-海风藤的活性成分和其对应的靶点。借助GeneCards数据库、DisGenet数据库获取HSPN的致病靶点。使用在线绘图工具微生信获得药物-疾病交集靶点,导入Cytoscape 3.9.1绘制“药物-主要活性成分-疾病-靶点”图。采用STRING数据库获取交集靶点的蛋白质-蛋白质相互作用(Protein-protein Interaction,PPI)网络信息,并通过CytoNCA插件筛选出治疗HSPN的核心靶点。利用Metascape数据库对交集靶点进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)富集分析,采用AutoDuck Vina对核心成分与核心靶点进行分子对接验证。结果:本研究筛选丹参-海风藤治疗HSPN的靶点47个,对应2个药物(丹参、海风藤)、74个活性成分(其中丹参56个活性成分、海风藤18个活性成分)。筛选出核心靶点15个,包括基质金属蛋白酶(Matrix Metalloproteinase,MMP)-9、白细胞介素(Interleukin,IL)-6、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、肿瘤蛋白p53(Tumor Protein p53,TP53)、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、MYC基因、信号转导因子和转录激活因子3(Signal Transducer and Activator of Transcription 3,STAT3)、半胱氨酸天冬氨酸酶(Caspase,CASP3)、过氧化物酶体增殖物激活受体γ(Peroxisome Proliferator Activated Receptor Gamma,PPARG)基因、前列素内环氧化物合成酶2(Prostaglandin-endoperoxide Synthase 2,PTGS2)、雌激素受体(Estrogen Receptor 1,ESR1)、淀粉样β前体蛋白(Amyloid Beta PrecurObjective:To discuss the mechanism of Danshen(Salvia miltiorrhiza)-Haifengteng(Futokadsura stem)on henoch schonlein purpura nephritis(HSPN)based on network pharmacology and“Blood-excess syndrome should be treated by removing therapy”theory.Methods“:Blood-excess syndrome should be treated by removing therapy”theory originates from Suwen《素问》,and it is the general principle of promoting blood circulation and removing stasis.Based on“Blood-excess syndrome should be treated by removing therapy”theory,Danshen-Haifengteng was selected as the research drug.The active ingredients of Danshen-Haifengteng were screened and their corresponding targets were obtained by TCM systematic pharmacology database and analysis platform(TCMSP).The pathogenic targets of HSPN were obtained by GeneCards database and DisGenet database.The online drawing tool Weishengxin was used to obtain the intersection target of drug and disease,and Cytoscape 3.9.1 was used to draw the map of“Drug-Main active ingredients-Disease-Target”.The proteinprotein interaction(PPI)network information of intersected targets was obtained by STRING database,and the core targets for HSPN treatment were screened by CytoNCA plug-in.Metascape database was used to perform GO enrichment analysis and KEGG enrichment analysis for intersection targets.AutoDuck Vina was used to verify the molecular docking between core ingredients and core targets.Results:In this study,47 therapeutic targets of Danshen-Haifengteng were screened,corresponding to 2 drugs(Danshen and Haifengteng)and 74 active ingredients(including 56 active ingredients of Danshen and 18 active ingredients of Haifengteng).A total of 15 core targets were screened,including matrix metalloproteinase-9(MMP9),interleukin-6(IL-6),serine protein kinase(AKT1),tumor necrosis factor(TNF),tumor suppressor gene P53(TP53),vascular endothelial growth factor A(VEGFA),MYC gene,transcription activator 3(STAT3),Caspase 3(CASP3),PPARG gene,cyclooxygenase 2(PTGS2),estrogen receptor(ESR1),amyloid beta precursor

关 键 词：紫癜性肾炎 丹参-海风藤 网络药理学 分子对接 

分 类 号：R256.5[医药卫生—中医内科学]