基于网络药理学预测射干治疗支气管哮喘作用机制

Prediction of She Ggan for Treatment of Bronchial Asthma Based on Network Pharmacology

目的:基于网络药理学预测射干治疗支气管哮喘的作用机制。方法:通过中药系统药理学技术平台(TCMSP)检索射干化学成分,Swiss Target Prediction数据库得到射干的预测靶点,通过Gene Cards数据库获取哮喘相关靶点将射干的预测靶点与哮喘相关靶点进行映射得到射干治疗哮喘的预测靶点。通过Cytoscape(3.6.0)软件,生成射干治疗哮喘的蛋白与蛋白相互作用(PPI)网络。通过DAVID网站(基因百科全书)进行KEGG通路分析,运用systems Dock网站对预测靶标与其对应的成分进行分子对接。结果:射干活性化合物有17种,筛选出射干可能与哮喘相关的靶点74个,关键靶点共16个,包括雌激素受体α(ESR1)、蛋白激酶C-α(PRKCA)、醛糖还原酶(AR)、蛋白激酶C-delta(PRKCD)、蛋白质激酶C-β(PRKCB)等。通过KEGG通路分析得到128条通路,结合文献检索,筛选出治疗哮喘的可能通路为20条,主要分为以下四类,①气道炎症相关通路:PI3K-Akt信号通路、趋化因子信号通路、MAPK信号通路等;②气道平滑肌相关通路:Ras信号通路、Hippo信号通路、钙信号通路等;③血管增生相关通路:VEGF信号通路;④免疫相关通路:T细胞受体信号通路、Toll样受体信号通路。结论:射干通过多靶点、多通路治疗哮喘,其机制可能与气道炎症相关通路、气道平滑肌相关通路、血管增生相关通路、免疫相关通路的作用相关。

Objective:To predict the mechanism of she ganShegan(Rhizoma Belamcandae) in the treatment of bronchial asthma based on network pharmacology. Methods:Based on the traditional Chinese medicine systems pharmacology database(TCMSP),the chemical compositions of Shegan decoction were obtained. The target related to asthma was obtained by GeneCards database,and the predicted target of Shegan was mapped to the target related to asthma to obtain the predictive target of Shegan in the treatment of asthma. The protein protein interaction(PPI) network in the treatment of asthma was generated by Cytoscape(3.6.0). Through DAVID website(Encyclopedia of genes) KEGG pathway analysis,using systems Dock website to predict the target and its corresponding components for molecular docking. Results:There were 17 kinds of active compounds. There were74 targets related to asthma screened out,including estrogen receptor 1(ESR1),protein kinase C alpha(PRKCA),aldose reductase(AR),protein kinase C delta(PRKCD),protein kinase C beta(PRKCB) and so on. Through the analysis of KEGG pathway,128 channels are obtained. There were 20 possible pathways in the treatment of asthma,which were divided into the following four categories:①Airway inflammation related pathway:PI3 K-Akt signaling pathway,chemokine signaling pathway,MAPK signaling pathway and so on. ②Airway smooth muscle related pathways:Ras signaling pathway,hippo signaling pathway,calcium signaling pathway. ③ Vascular proliferation related pathway:VEGF signaling pathway. ④ Immune related pathways:T cell receptor signaling pathway,toll-like receptor signaling pathway. Conclusion:Shegan treats asthma through multiple targets and pathways,and it may play a role in airway inflammation related pathways,airway smooth muscle related pathways,vascular proliferation related pathways and immune related pathways.