目的 網(wǎng)絡藥理學結合分子對接技術探索展筋活血散治療軟組織損傷的分子調(diào)控機制，為展筋活血散的臨床使用提供數(shù)據(jù)支撐。方法 運用TCMSP、ETCM、BATMAN-TCM數(shù)據(jù)庫收集展筋活血散成分和靶點，同時GeneCards和OMIM數(shù)據(jù)庫獲取軟組織損傷的靶點。將成分與疾病靶點取交集獲得展筋活血散治療軟組織損傷主要成分和靶點，采用Cytoscape軟件構建展筋活血散治療軟組織損傷的活性成分和交集靶點網(wǎng)絡圖。STRING數(shù)據(jù)庫構建交集靶點的蛋白相互作用（PPI）網(wǎng)絡圖，微生信和歐易云平臺用于開展基因本體（GO）和京都基因與基因組百科全書（KEGG）富集分析。采用分子對接技術驗證展筋活血散治療軟組織損傷的關鍵成分和靶點的結合強弱。結果 本研究篩選出展筋活血散40種活性成分（人參皂苷Rh₂、血竭素、大豆黃素、槲皮素、山柰酚、黃柏苷和阿魏酸松柏酯等），靶向軟組織損傷的48個靶點[（免疫炎癥因子白細胞介素（IL）-3、IL-4、IL-6、Toll樣受體4（TLR4）、腫瘤壞死因子（TNF）、前列腺素內(nèi)過氧化物合酶2（PTGS2），血管新生因子血管內(nèi)皮生長因子A（VEGFA）、一氧化氮合成酶3（NOS3）和血紅素加氧酶1（HMOX1），凋亡因子半胱氨酸天冬氨酸蛋白酶3（CASP3）、CASP8，激素調(diào)控因子雌激素受體1（ESR1）等]，參與低氧誘導因子-1（HIF-1）、磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B1（Akt）、IL-17、TNF和甲狀腺激素信號通路等15條通路。分子對接證實展筋活血散的活性成分與其對應的軟組織損傷靶點結合力較強。結論 展筋活血散通過人參皂苷Rh₂、血竭素、大豆黃素、槲皮素、山柰酚、黃柏苷和阿魏酸松柏酯等活性成分靶向IL-6、TLR4、TNF、CASP3、VEGFA和ESR1等關鍵靶點發(fā)揮治療軟組織損傷的功效。

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

新疆維吾爾自治區(qū)衛(wèi)生健康適宜技術推廣項目(SYTG-Y202423)