目的 网络药理学结合分子对接技术探索展筋活血散治疗软组织损伤的分子调控机制，为展筋活血散的临床使用提供数据支撑。方法 运用TCMSP、ETCM、BATMAN-TCM数据库收集展筋活血散成分和靶点，同时GeneCards和OMIM数据库获取软组织损伤的靶点。将成分与疾病靶点取交集获得展筋活血散治疗软组织损伤主要成分和靶点，采用Cytoscape软件构建展筋活血散治疗软组织损伤的活性成分和交集靶点网络图。STRING数据库构建交集靶点的蛋白相互作用（PPI）网络图，微生信和欧易云平台用于开展基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。采用分子对接技术验证展筋活血散治疗软组织损伤的关键成分和靶点的结合强弱。结果 本研究筛选出展筋活血散40种活性成分（人参皂苷Rh₂、血竭素、大豆黄素、槲皮素、山柰酚、黄柏苷和阿魏酸松柏酯等），靶向软组织损伤的48个靶点[（免疫炎症因子白细胞介素（IL）-3、IL-4、IL-6、Toll样受体4（TLR4）、肿瘤坏死因子（TNF）、前列腺素内过氧化物合酶2（PTGS2），血管新生因子血管内皮生长因子A（VEGFA）、一氧化氮合成酶3（NOS3）和血红素加氧酶1（HMOX1），凋亡因子半胱氨酸天冬氨酸蛋白酶3（CASP3）、CASP8，激素调控因子雌激素受体1（ESR1）等]，参与低氧诱导因子-1（HIF-1）、磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B1（Akt）、IL-17、TNF和甲状腺激素信号通路等15条通路。分子对接证实展筋活血散的活性成分与其对应的软组织损伤靶点结合力较强。结论 展筋活血散通过人参皂苷Rh₂、血竭素、大豆黄素、槲皮素、山柰酚、黄柏苷和阿魏酸松柏酯等活性成分靶向IL-6、TLR4、TNF、CASP3、VEGFA和ESR1等关键靶点发挥治疗软组织损伤的功效。

Objective The molecular regulatory mechanism of Zhanjin Huoxue Powder in treatment of soft tissue injury was initially explored by network pharmacology combined with molecular dock technology, which provided data support for the clinical use of Zhanjin Huoxue Powder. Methods TCMSP, ETCM and BATMAN-TCM databases were used to collect the components and targets of Zhanjin Huoxue Powder, while GeneCards and OMIM databases were used to obtain the targets of soft tissue injury. The main components and targets of Zhanjin Huoxue Powder in treatment of soft tissue injury were obtained by intersection of components and disease targets. The active components and intersection target network of Zhanjin Huoxue Powder for the treatment of soft tissue injury were constructed by Cytoscape software. The PPI network map of intersecting targets was constructed in STRING database, which was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis by Weisheng and Ouyi Cloud platforms. Molecular docking technology was used to verify the combination strength of key components and targets of Zhanjin Huoxue Powder in treatment of soft tissue injury. Results In this study, 40 active components of Zhanjin Huoxue Powder (ginsenoside Rh₂, dracorhodin, daidzein, quercetin, kaempferol, phellamurin and coniferyl ferulate) were screened for 48 targets (immunoinflammatory cytokines IL-3, IL-4, IL-6, TLR4, TNF, and PTGS2; angiogenesis factors VEGFA, NOS3, and HMOX1; apoptosis factors CASP3, CASP8; hormone regulatory factors ESR1) and HIF-1, PI3K/Akt, IL-17, TNF, and 15 thyroid hormone signaling pathways involved in soft tissue injury. Molecular docking proved that the active components of Zhanjin Huoxue Powder had strong binding force with the corresponding soft tissue injury targets. Conclusion Zhanjin Huoxue Powder can treat soft tissue injury by targeting key targets IL-6, TLR4, TNF, CASP3, VEGFA, and ESR1 through ginsenoside Rh₂, dracorhodin, daidzein, quercetin, kaempferol, phellamurin, and coniferyl ferulate.

R982

新疆维吾尔自治区卫生健康适宜技术推广项目(SYTG-Y202423)