| 摘要: |
| 目的：通过网络药理学和分子对接技术探讨芪冬活血饮治疗肺纤维化(pulmonary fibrosis,PF）的潜在机制。方法：通过中药系统药理学(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP）、本草组鉴(a High-Throughput Experiment-and-Reference-Guided Database of Traditional Chinese Medicine,HERB）数据库检索出芪冬活血饮中各中药的主要活性化学成分及其对应的靶点，并借助人类基因数据库(Genecards Human Gene Database,GeneCards）、基因疾病关联(Disease Gene Network,DisGeNET）数据库收集PF疾病相关的靶点基因。使用Venny、蛋白质相互作用数据库(Search Tool for the Retrieval of Interacting Genes/Proteins,STRING）和Cytoscape分析共同靶点并构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI）网络。利用基因功能注释与集成分析数据库(Database for Annotation，Visualization and Integrated Discovery,DAVID）进行共同靶点的基因本体(gene ontology,GO）功能、京都基因与基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG）通路富集分析。运用AutoDock软件进行分子对接模拟，验证研究结果。结果：芪冬活血饮包含34个活性成分及221个潜在作用靶点，其中有131个靶点与PF相关基因重叠。筛选出包括肿瘤坏死因子(tumor necrosis factor,TNF）、白细胞介素-6(interleukin-6,IL-6）、白细胞介素-1β(interleukin-1 beta,IL-1β）等10个核心靶点。GO功能和KEGG通路分析发现，芪冬活血饮通过参与调节基因表达、细胞增殖和凋亡等生物过程，调控高级糖基化终产物/受体(advanced glycation end products/receptor for advanced glycation end products,AGE/RAGE）、白细胞介素17(interleukin-17,IL-17）、TNF、磷脂酰肌醇3激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein pinase B,PI3K/Akt）等信号通路对PF发挥治疗作用。分子对接结果表明，活性成分与核心靶点之间具有较强的结合亲和力，进一步支持了其药理学的相关性。结论：本研究揭示了芪冬活血饮可能通过干预AGE/RAGE、IL-17、TNF、PI3K/Akt等信号通路，影响炎症因子网络，减少成纤维细胞异常增殖及细胞外基质(extracellular matrix,ECM）过度沉积，从而缓解PF病理损伤，为后续研究和开发新型治疗策略提供了科学依据。 |
| 关键词: 肺纤维化 芪冬活血饮 网络药理学 分子对接 作用机制 |
| DOI： |
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| Mechanism of action of Qidong Huoxue decoction in treatment of pulmonary fibrosis:A study based on network pharmacology and molecular docking |
| ZHANG Ming,GAO Rundi,HONG Huihua |
| (The First School of Clinical Medicine of Zhejiang Chinese Medical University，Hangzhou 310053，Zhejiang，China;The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine），Hangzhou 310006，Zhejiang，China) |
| Abstract: |
| Objective: To investigate the potential mechanism of Qidong Huoxue decoction in the treatment of pulmonary fibrosis (PF） based on network pharmacology and molecular docking.Methods: TCMSP and HERB databases were used to obtain the main active components of each traditional Chinese medicine drug in Qidong Huoxue decoction and their corresponding targets，and GeneCards and DisGeNET databases were used to obtain the target genes associated with PF.Venny，STRING，and Cytoscape were used to analyze the common targets and construct a protein-protein interaction network.DAVID database was used to perform the gene ontology (GO） functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG） pathway enrichment analysis of the common targets.AutoDock software was used for molecular docking to verify research findings.Results: A total of 34 active components and 221 potential action targets were obtained for Qidong Huoxue decoction，among which 131 targets were overlapped with the genes associated with PF.A total of 10 core targets were obtained，including tumor necrosis factor (TNF），interleukin-6 (IL-6），and interleukin-1β (IL-1β）.The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that Qidong Huoxue decoction exerted a therapeutic effect on PF by regulating gene expression，cell proliferation，apoptosis，and the signaling pathways including the advanced glycation end products/receptor for advanced glycation end products (AGE/RAGE） signaling pathway，the interleukin-17 (IL-17） signaling pathway，the TNF signaling pathway，and the phosphatidylinositol 3-kinase/protein pinase B (PI3K/Akt） signaling pathway.Molecular docking showed relatively strong binding affinity between the active components and the core targets，which provided support for pharmacological relevance.Conclusion: This study shows that Qidong Huoxue decoction can affect inflammatory factor network，reduce abnormal proliferation of fibroblasts and excessive deposition of extracellular matrix，and alleviate the pathological injury of PF by regulating the AGE/RAGE，IL-17，TNF，and PI3K/Akt signaling pathways，which provides a scientific basis for subsequent research and development of new treatment strategies. |
| Key words: pulmonary fibrosis Qidong Huoxue decoction network pharmacology molecular docking mechanism of action |
