基于p38MAPK/NF-κB信号通路的麻黄汤抗哮喘作用机制研究

The anti-asthma effect of Mahuang decoction basedon p38MAPK/NF-κB signaling pathway and its mechanism

目的基于p38MAPK/NF-κB信号通路,探讨麻黄汤对哮喘大鼠气道重塑、气道高反应的改善作用。方法首先通过网络药理学筛选麻黄汤治疗哮喘的潜在信号通路,然后复制哮喘大鼠模型,检测气道反应性,观察麻黄汤给药后大鼠气道粘液分泌及胶原沉积情况,检测大鼠血清中相关指标含量和肺组织中关键基因水平。结果网络药理学共筛选出麻黄汤186个候选靶点,通路分析发现其治疗哮喘的机制主要涉及Toll样受体、MAPK、T细胞受体等。麻黄汤可降低哮喘大鼠气道反应性,减少气道杯状细胞分泌,改善气道上皮下胶原沉积情况;并可降低血清中VEGF、TGF-β1、ET-1、OPN、bFGF的分泌,抑制大鼠因OVA致敏激发而上调的p38MAPK、NF-κB p65、VEGF mRNA表达量。结论麻黄汤可降低哮喘大鼠气道反应性,改善气道重塑情况,其机制可能与下调VEGF、TGF-β1、ET-1、OPN、bFGF含量以及p38MAPK/NF-κB信号通路上的关键基因表达有关。

Aim To explore the intervention effect of Mahuang decoction on airway remodeling and airway hyperresponsiveness in asthmatic rats based on the p38MAPK/NF-κB signaling pathway.Methods Network pharmacology was used to screen the potential signaling pathway of Mahuang decoction in treating asthma.The asthma model was replicated,and the airway reactivity and the pathologic changes of lung tissues of rats were observed.The concentrations of related indexes in rat serum and the expressions of key genes in murine pulmonary tissues were assessed.Results The results of network pharmacology identified 186 candidate targets,and pathway analysis showed that the treatment mechanism for asthma mainly involved Toll like receptor,mitogen activated protein kinase(MAPK),T cell receptor and so on.Mahuang decoction reduced the airway mucus secretion,attenuated the subcutaneous collagen deposition in the airway,and decreased the airway reactivity significantly.It also obviously inhibited the concentrations of VEGF,TGF-β1,ET-1,OPN and bFGF in rat serum,and the mRNA expressions of p38MAPK,NF-κBp65 and VEGF in murine pulmonary tissues.Conclusions Mahuang decoction can reduce the airway mucus secretion and attenuate the asthma airway remodeling,which may be related to its abilities of adjusting the concentrations of VEGF,TGF-β1,ET-1,OPN,bFGF,and the expressions of key genes in p38MAPK/NF-κB signaling pathway.