基于网络药理学的痹祺胶囊治疗类风湿性关节炎的配伍规律研究  

Compatibility rule of Biqi Capsule in treatment of rheumatoid arthritis based on network pharmacology

作　　者：李新 韩彦琪[1,2,3] 张祥麒 许浚[1,2,3] 王春芳 王磊 张铁军[1,2,3] 刘昌孝[1,2,3] LI Xin;HAN Yan-qi;ZHANG Xiang-qi;XU Jun;WANG Chun-fang;WANG Lei;ZHANG Tie-jun;LIU Chang-xiao(Tianjin Key Laboratory of Quality Marker of Traditional Chinese Medicine,Tianjin Institute of Pharmaceutical Research,Tianjin 300462,China;National&Local United Engineering Laboratory of Modern Preparation and Quality Control Technology of Traditional Chinese Medicine,Tianjin Institute of Pharmaceutical Research,Tianjin 300462,China;National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine,Tianjin Institute of Pharmaceutical Research,Tianjin 300462,China;Tianjin Darentang Jingwanhong Pharmaceutical Co.,Ltd.,Tianjin 300112,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin Pharmaceutical Da Ren Tang Group Co.,Ltd.,Tianjin 300193,China)

机构地区：[1]天津药物研究院,天津市中药质量标志物重点实验室,天津300462 [2]天津药物研究院,中药现代制剂与质量控制技术国家地方联合工程实验室,天津300462 [3]天津药物研究院,药物成药性评价与系统转化全国重点实验室,天津300462 [4]天津达仁堂京万红药业有限公司,天津300112 [5]天津中医药大学,天津301617 [6]津药达仁堂集团股份有限公司,天津300193

出　　处：《中草药》2023年第23期7607-7617,共11页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金重点项目(U21A20406)。

摘　　要：目的 基于网络药理学方法探讨痹祺胶囊的配伍规律,阐释其治疗类风湿性关节炎(rheumatoid arthritis,RA)的机制内涵。方法 按照痹祺胶囊及其单味药材的功效将其分为益气养血组、活血通络组、抗炎镇痛组,并分别选取药材中的特征成分,依据反向药效团匹配方法和TCMSP、Uniprot等数据库预测化合物作用靶点,与通过OMIM、DisGeNet、GeneCards等数据库收集RA相关靶点相互交互,将交互靶点借助Omicsbean、STRING等数据库平台对获得靶点进行基因本体功能和京都基因与基因组百科全书通路富集分析,利用Cytoscape软件构建“药材-化合物-靶点-通路-功效”网络。结果 通过网络药理学预测,得到益气养血组11个成分的67个潜在靶点,蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络分析发现白蛋白、肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-6(interleukin-6,IL-6)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、造血前列腺素合成酶D、丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、雄激素受体、β2肾上腺素能受体等可能为关键核心靶点,主要通过神经营养信号通路、造血细胞谱系、破骨细胞分化、MAPK信号通路等40条相关通路,通过调控骨髓造血微环境、骨形成与代谢平衡、免疫调节等生物过程发挥益气养血作用;得到活血通络组20个成分的117个潜在靶点,进一步PPI网络分析发现蛋白激酶B1(protein kinase B1,AKT1)、基质金属蛋白酶9(matrix metalloproteinase 9,MMP9)、肿瘤蛋白p53(tumor protein p53,TP53)、纤连蛋白、信号转导子和转录激活子3、C-C基序趋化因子(C-C motif chemokine 2,CCL2)、表皮生长因子受体、细胞间黏附分子1、IL17A等可能为核心靶点,并通过血小板激活、VEGF信号通路、IL-17信号通路等77条相关通路调控凝血和纤溶系统、血管增生、抗炎镇痛等生物过程发挥活血通络、�Objective To explore the compatibility regularity of Biqi Capsule(痹祺胶囊)and elucidate the mechanism and connotation of its treatment of rheumatoid arthritis based on network pharmacology.Methods According to the efficacy of Biqi Capsule and its single medicinal materials,it was divided into supplementing qi and nourishing blood group,promoting blood circulation and dredging collaterals group and anti-inflammatory and analgesic group,and the characteristic components in the medicinal materials were selected respectively,and the target of the compound was predicted according to the reverse pharmacophore matching method and databases such as TCMSP and Uniprot.With the help of database platforms such as Omicsbean and STRING,the interactive targets were analyzed by gene ontology function and Kyoto encyclopedia of genes and genomes pathway(KEGG),and“medicinal material-compound-target-pathway-efficacy”network was constructed by Cytoscape software.Results Through the prediction of network pharmacology,a total of 67 potential targets of 11 components in supplementing qi and nourishing blood group were obtained,protein-protein interaction(PPI)network analysis found that albumin(ALB),tumor necrosis factor(TNF),interleukin-6(IL-6),vascular endothelial growth factor A(VEGFA),hematopoietic prostaglandin D synthase(HPGDS),mitogen-activated protein kinase 1(MAPK1),androgen receptor(AR),Beta-2 adrenergic receptor(ADRB2),etc.may be the key core targets,mainly played a role in invigorating qi and nourishing blood by regulating biological processes such as bone marrow hematopoietic microenvironment,bone formation and metabolic balance,and immune regulation,through 40 related pathways such as neurotrophic signaling pathway,hematopoietic cell lineage,osteoclast differentiation,MAPK signaling pathway,etc.A total of 117 potential targets of 20 components in promoting blood circulation and dredging collaterals group were obtained,and further PPI network analysis showed that protein kinase B1(AKT1),matrix metalloprotease 9(MMP9

关 键 词：痹祺胶囊 类风湿性关节炎 配伍规律 益气养血 活血通络 抗炎镇痛 

分 类 号：R285.5[医药卫生—中药学]