基于网络药理学和实验验证研究射干–麻黄对支气管炎的免疫调节作用

Study on Immunomodulatory Effect of Belamcandae Rhizoma and Ephedrae Herba on Bronchitis Based on Network Pharmacology and Experimental Verification

摘要: 目的：通过网络药理学的研究方法和分子对接技术探索射干–麻黄药对支气管炎的作用机制。方法：使用中药系统药理数据分析平台(TCMSP)检索射干和麻黄的活性成分。使用Gene Cards数据库筛选支气管炎疾病作用靶点，应用STRING数据库和Cytoscape构建射干和麻黄与支气管炎的作用靶点网络和蛋白互作网络(PPI)以寻找关键作用靶点。使用Autodock Vina对射干–麻黄的核心成分与关键作用靶点进行分子对接验证。运用DAVID (v6.8)数据库对关键作用靶点进行基因本体(GO)和基因组数据库(KEGG)通路富集分析。结果：射干–麻黄药对的主要活性成分为槲皮素，木犀草素、山奈酚，柚皮素和异鼠李素，作用于支气管炎的关键靶点是TNF、IL-6、IL-1B、MAPK1和VEGFA。分子对接验证结果显示核心成分能与关键作用靶点充分结合而发挥作用，候选靶点主要富集TNF信号通路、HIF-1信号通路、FoxO信号通路和NOD样受体信号通路。射干–麻黄药对可降低支气管肺炎大鼠血中免疫蛋白IgA、IgM、IgG以及免疫因子IL-1、IL-6和TNF-a的含量。结论：射干–麻黄药对主要的活性成分为槲皮素，木犀草素、山奈酚，柚皮素和异鼠李素，它调控TNF信号通路、HIF-1信号通路、FoxO信号通路和NOD样受体等信号通路降低免疫因子来发挥治疗支气管炎的作用。

Abstract: Objective: To explore the molecular mechanism of Belamcandae Rhizoma and Ephedrae Herba cou-plet medicines (BREHCM) on bronchitis based on molecular docking technology and network pharmacology. Methods: The active components were searched using the traditional Chinese Medi-cine Systems Pharmacology Database Analysis Platform (TCMSP). Gene Cards database was used to screen bronchitis disease targets. The STRING database and Cytoscape were applied to construct the couplet medicines with bronchitis action target network and protein interaction network (PPI). Molecular docking validation of the core components with key targets was performed using Auto-dock Vina. David (v6.8) was used to perform target Gene Ontology (GO) and KEGG pathway analysis. Results: The main active components of BREHCM are quercetin, luteolin, kaempferol, naringin and isorhamnetin. The key targets for bronchitis are TNF, IL-6, IL-1B, mapk1 and VEGFA. The results of molecular docking verification show that the core components can fully combine with the key tar-gets and play a role. Candidate targets mainly enrich TNF signaling pathway, HIF-1 signaling path-way, FoxO signaling pathway and nod like receptor signaling pathway. BREHCM can reduce the contents of immune proteins IgA, IgM, IgG and immune factors IL-1, IL-6 and TNF-a in the blood of rats with bronchopneumonia. Conclusion: The core active ingredients of BREHCM are quercetin, lu-teolin, kaempferol, naringenin, and isorhamnetin, which may regulate TNF signaling pathway, HIF-1 signaling pathway, FoxO signaling pathway, and NOD-like receptor signaling pathway to exert therapeutic effects on bronchitis.