医药导报2026，Vol.45Issue(4)：581-588,8.DOI:10.3870/j.issn.1004-0781.2026.04.004
丹参酮ⅡA通过p38MAPK/NF-κB和AKT/HIF-1α信号通路改善哮喘小鼠气道炎症和气道重塑
Tanshinone IIA Ameliorates Airway Inflammation and Remodeling in Asthmatic Mice via the p38 MAPK/NF-κB and AKT/HIF-1α Signaling Pathways
摘要
Abstract
Objective To investigate the effect and mechanism of Tanshinone ⅡA(TanⅡA)on airway inflammation and remodeling in the ashmatic mice.Methods Female BALB/c mice aged 7-8 weeks were divided into three groups:control,model,and TanⅡA group.An asthma model was established using ovalbumin(OVA)sensitization and challenge.10 mg•kg-1 TanⅡA administration began on the third day post-sensitization via oral gavage twice daily for seven consecutive days.The proportions of eosinophils,neutrophils,and monocytes in bronchoalveolar lavage fluid(BALF)were analyzed.Levels of IL-4,IL-5,IL-13,VEGF,and TGFβ1 in BALF were measured by ELISA.Histopathological changes in lung tissues were examined by HE staining;collagen deposition by Masson trichrome staining;goblet cell hyperplasia and mucus secretion by PAS staining.Western blotting was used to detect the expression levels of p38MAPK,p-p38 MAPK,MMP9,AKT,p-AKT,and Collagen Ⅰ.Immunohistochemistry was performed to assess the expression of HIF-1α and NF-κB p65 in lung tissues.Molecular docking tested the binding affinity between TanⅡA and MAPK as well as AKT.Results Compared with the control group,the model group exhibited significantly increased levels of inflammatory cytokines and cellular ratios in BALF(P<0.01),along with evident pulmonary tissue damage,collagen deposition,and goblet cell hyperplasia with excessive mucus production.Administration of TanⅡA markedly reversed these phenomena(P<0.05).Moreover,TanⅡA treatment downregulated the expression of key proteins in the MAPK/NF-κB and AKT/HIF-1α signaling pathways.Additionally,the binding energies of TanⅡA with p38 MAPK and AKT were-27.53 and-28.12 kJ•mol-1,respectively,indicating good binding capabilities.Conclusion TanⅡA can significantly alleviate airway inflammation and remodeling in asthmatic mice,characterized by reduced secretion of inflammatory cytokines and decreased ratios of eosinophils,monocytes,and neutrophils,as well as mitigated pathological injury in lung tissues.Its mechanism may involve inhibition of the p38 MAPK/NF-κB and AKT/HIF-1α signaling pathways.关键词
丹参酮ⅡA/气道炎症/气道重塑/哮喘/p38MAPK/NF-κB信号通路/AKT/HIF-1α信号通路Key words
Tanshinone Ⅱ A/Airway inflammation/Airway remodeling/Asthma/p38 MAPK/NF-κB signaling pathway/AKT/HIF-1α signaling pathway分类
医药卫生引用本文复制引用
朱佳聪,彭震震,梅惠娅,余炜杰,陈俊国..丹参酮ⅡA通过p38MAPK/NF-κB和AKT/HIF-1α信号通路改善哮喘小鼠气道炎症和气道重塑[J].医药导报,2026,45(4):581-588,8.基金项目
浙江省医药卫生科技计划项目(2023KY335). （2023KY335）
