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OA
Tanshinone IIA Ameliorates Airway Inflammation and Remodeling in Asthmatic Mice via the p38 MAPK/NF-κB and AKT/HIF-1α Signaling Pathways
目的 研究丹参酮ⅡA(TanⅡA)对哮喘小鼠气道炎症及重塑的影响及其分子机制.方法 选取 7～8 周龄雌性 BALB/c 小鼠,随机分为 3 组:对照组、模型组和 TanⅡA 组.通过卵清蛋白(OVA)致敏与激发建立哮喘模型.从致敏后第 3 天开始,小鼠灌胃给予 10 mg•kg-1 TanⅡA,每日 2 次,连续7 d.分析支气管肺泡灌洗液(BALF)中嗜酸性粒细胞、中性粒细胞及单核细胞的比例;使用 ELISA 检测 BALF 中白细胞介素(IL)-4、IL-5、IL-13、小鼠血管内皮生成因子(VEGF)和小鼠转化生长因子 β1(TGFβ1)的水平.通过 HE 染色检查肺组织的组织病理学变化;Masson 三色染色评估胶原沉积;PAS 染色观察杯状细胞增生及黏液分泌情况.Western blotting 用于检测 p38 MAPK、p-p38 MAPK、基质金属蛋白酶 9(MMP9)、蛋白激酶 B(AKT)、p-AKT 和 CollagenⅠ的表达水平.免疫组化法评估肺组织中 HIF-1α 和 NF-κB p65的表达.分子对接检测 TanⅡA 与 p38 MAPK 和 AKT 的结合情况.结果 模型组小鼠炎性细胞因子水平和炎性细胞比例显著升高(P<0.01),肺组织损伤、胶原沉积和杯状细胞增生明显.TanⅡA 干预显著逆转了这些现象(P<0.05),并且下调了 MAPK/NF-κB 和 AKT/HIF-1α 信号通路中关键蛋白的表达,此外,TanⅡA 与 p38 MAPK 和 AKT 的结合能分别为-27.53和-28.12 kJ•mol-1,表明具有良好结合能力.结论 TanⅡA 可以显著改善哮喘小鼠的气道炎症和重塑,减少炎性细胞因子分泌,减轻肺部病理性损伤,其作用机制可能涉及抑制 p38MAPK/NF-κB 和 AKT/HIF-1α 信号通路.
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.
朱佳聪;彭震震;梅惠娅;余炜杰;陈俊国
嘉兴市第二医院儿科,嘉兴 314000嘉兴市第二医院儿科,嘉兴 314000嘉兴市第二医院儿科,嘉兴 314000嘉兴市第二医院儿科,嘉兴 314000嘉兴市第二医院儿科,嘉兴 314000||嘉兴大学医学院,嘉兴 314001
医药卫生
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
Tanshinone Ⅱ AAirway inflammationAirway remodelingAsthmap38 MAPK/NF-κB signaling pathwayAKT/HIF-1α signaling pathway
《医药导报》 2026 (4)
581-588,8
浙江省医药卫生科技计划项目(2023KY335).
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