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、止痛的作用；得到抗炎镇痛组8个成分的180个潜在靶点，进一步PPI网络分析发现TNF、AKT1、IL-6、TP53、IL1B、VEGFA、前列腺素G/H合成酶2、CCL4、CCL3等可能为潜在核心靶点，通过IL-17信号通路、T和B细胞受体信号通路、血清素能突触、趋化因子信号通路、核因子-κB信号通路、花生四烯酸代谢等77条通路干预中枢和外周敏化、抗原呈递、免疫细胞激活、炎症反应等生物过程发挥抗炎镇痛的作用。结论 痹祺胶囊中党参、茯苓、白术组成的益气养血组主要在造血系统、免疫系统和骨形成和代谢等方面发挥“固本”的作用，丹参、三七、川芎、牛膝、地龙组成的活血通络组主要在血液系统、炎症反应等方面发挥“活血化瘀”的作用，马钱子、甘草组成的抗炎镇痛组主要在免疫调控、炎症反应、中枢和外周镇痛等方面发挥“除湿止痛”的作用，各组之间的靶点和通路互有交叉，又各有侧重，充分体现了痹祺胶囊在治疗RA中多成分、多靶点、多通路的特点，为其配伍理论的深入研究奠定了基础。

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), tumor protein p53 (TP53), fibronectin (FN1), signal transducer and activator of transcription 3 (STAT3), C-C motif chemokine 2 (CCL2), epidermal growth factor receptor (EGFR), intercellular adhesion molecule 1 (ICAM1), IL17A, etc. may be the core targets, and mainly played a role in promoting blood circulation and dredging collaterals and relieving pain by regulating coagulation and fibrinolysis system, vascular proliferation and anti-inflammatory and analgesic processes through 77 related pathways such as platelet activation, VEGF signaling pathway and IL-17 signaling pathway. A total of 180 potential targets of eight components in anti-inflammatory and analgesic group were obtained, and further PPI network analysis found that TNF, AKT1, IL-6, TP53, IL1B, VEGFA, prostaglandin G/H synthetase 2, CCL4, CCL3, etc. might be potential core targets. Through 77 pathways, such as IL-17 signaling pathway, T and B cell receptor signaling pathway, serotonergic synapse, chemokine signaling pathway, nuclear factor-κB signaling pathway, arachidonic acid metabolism, etc., it plays an anti-inflammatory and analgesic role by interfering with biological processes such as central and peripheral sensitization, antigen presentation, immune cell activation, inflammatory reaction. Conclusion The supplementing qi and nourishing blood group composed of Dangshen (Codonopsis Radix), Fuling (Poria) and Baizhu (Atractylodis Macrocephalae Rhizoma) in Biqi Capsule mainly plays the role of “consolidating the foundation” in hematopoietic system, immune system, bone formation and metabolism, while the promoting blood circulation and dredging collaterals group composed of Dangshen (Salviae Miltiorrhizae Radix et Rhizoma), Sanqi (Notoginseng Radix et Rhizoma), Chuanxiong (Chuanxiong Rhizoma), Niuxi (Achyranthis Bidentatae Radix) and Dilong (Pheretima) mainly plays the role of “promoting blood circulation and removing blood stasis” in blood system and inflammatory reaction. The anti-inflammatory and analgesic group composed of Maqianzi (Strychni Semen) and Gancao (Glycyrrhrizae Radix et Rhizoma) mainly plays the role of “dehumidification and analgesia” in immune regulation, inflammatory reaction, central and peripheral analgesia, etc. The targets and pathways of each group intersect with each other, and each group has its own emphasis, which fully embodies the characteristics of Biqi Capsule in treating RA with multiple components, multiple targets and multiple pathways, and lays a foundation for the in-depth study of its compatibility theory.

R285.5

国家自然科学基金重点项目（U21A20406）