首页|期刊导航|中医儿科杂志|从缺氧诱导因子-1α表达的变化探讨平喘Ⅰ号治疗支气管哮喘模型小鼠的作用机制研究

从缺氧诱导因子-1α表达的变化探讨平喘Ⅰ号治疗支气管哮喘模型小鼠的作用机制研究OA

Study on the Mechanism of Anti-Asthma Formula Ⅰ in Treating Bronchial Asthma Model Mice from the Perspective of Hypoxia-Inducible Factor-1α Expression Changes

中文摘要英文摘要

目的 观察中药平喘Ⅰ号方对支气管哮喘模型小鼠肺组织内缺氧诱导因子-1α(HIF-1α)的表达变化及影响,探讨该药治疗支气管哮喘的作用机制.方法 72只4~6周龄的小鼠随机分为正常对照组、模型对照组、布地奈德治疗组、平喘Ⅰ号低剂量组、平喘Ⅰ号中剂量组、平喘Ⅰ号高剂量组,各12只.使用腹腔注射卵清蛋白(OVA)以及雾化吸入方式造模,然后予以生理盐水,布地奈德雾化液及中药平喘Ⅰ号低、中、高3种剂量介入.3周后获取哮喘小鼠的肺组织,观察病理切片,并利用图像分析软件测定支气管壁厚度(Wat)以及平滑肌厚度(Wam),采用实时定量-聚合酶链反应(Realtime-PCR)检测小鼠HIF-1α mRNA表达,免疫印迹法(Western blotting)检测小鼠HIF-1α蛋白表达.结果 正常对照组小鼠支气管管腔光滑,无闭塞,肺组织呈现完整的结构状态,肺泡结构清晰可见,无炎症水肿等反应;与正常对照组比较,模型组小鼠支气管管腔变窄,部分可见明显闭塞,出现炎症细胞聚集,肺泡形态受损,甚至肺泡内出现水肿样改变;治疗后平喘Ⅰ号各剂量组和布地奈德治疗组肺组织的炎症反应均有缓解,支气管管腔堵塞较模型对照组均有好转.与正常对照组比较,模型对照组的Wat与Wam显著升高,2组比较,差异有统计学意义(P<0.01);各治疗组显著低于模型对照组,差异均有统计学意义(P<0.01或P<0.05);平喘Ⅰ号高剂量组显著低于布地奈德治疗组和平喘Ⅰ号中、低剂量组,差异均有统计学意义(P<0.05),而平喘Ⅰ号中、低剂量组与布地奈德治疗组比较,差异无统计学意义(P>0.05).与正常对照组比较,模型对照组的HIF-1α mRNA及蛋白表达水平显著升高,2组比较,差异均有统计学意义(P<0.01);各治疗组显著低于模型对照组,差异均有统计学意义(P<0.01或P<0.05);平喘Ⅰ号高剂量组显著低于布地奈德治疗组和平喘Ⅰ号中、低剂量组,差异均有统计学意义(P<0.05),而平喘Ⅰ号中、低剂量组与布地奈德治疗组比较,差异无统计学意义(P>0.05).结论 HIF-1α在哮喘气道重塑中发挥了重要作用,平喘Ⅰ号能够通过下调HIF-1α的表达,抑制气道炎症和重塑,改善哮喘症状;高剂量的平喘Ⅰ号在抑制HIF-1α表达和改善气道重塑方面优于布地奈德,具有潜在的临床应用价值.

Objective To observe the changes and effects of the traditional Chinese medicine Anti-Asthma Formula Ⅰ on the expression of Hypoxia-Inducible Factor-1α(HIF-1α)in lung tissue of bronchial asthma mice,and to explore its mechanism in treating bronchial asthma.Methods Seventy-two 4-6 week-old mice were ran-domly divided into a normal control group,a model control group,a budesonide treatment group,an Anti-Asthma Formula Ⅰ low-dose group,an Anti-Asthma Formula Ⅰ medium-dose group,and an Anti-Asthma FormulaⅠ high-dose group,with 12 mice in each group.A model was established using intraperitoneal injection of ovalbu-min(OVA)and aerosol inhalation.Interventions were then administered with normal saline,budesonide aerosol solution,and three doses(low,medium,high)of Anti-Asthma Formula Ⅰ.After 3 weeks,lung tissue from asth-matic mice was obtained.Pathological sections were observed,and image analysis software was used to measure bronchial wall thickness(Wat)and airway smooth muscle thickness(Wam).Realtime quantitative polymerase chain reaction(Realtime-PCR)was employed to detect HIF-1α mRNA expression,and Western blotting was used to detect HIF-1α protein expression.Results In the normal control group,mouse bronchial lumens were smooth without occlusion,lung tissue showed intact structure,alveolar structure was clearly visible,and there were no inflammatory or edematous reactions.Compared with the normal control group,the model group exhibited narrowed bronchial lumens with some showing significant occlusion,inflammatory cell aggregation,damaged al-veolar morphology,and even edema-like changes within alveoli.After treatment,all Anti-Asthma Formula Ⅰ dose groups and the budesonide treatment group showed alleviated inflammatory reactions in lung tissue,and bron-chial lumen obstruction improved compared to the model group.Compared with the normal control group,Wat and Wam in the model control group were significantly increased,with a statistically significant difference be-tween the two groups(P<0.01).All treatment groups were significantly lower than the model control group,with statistically significant differences(P<0.01 or P<0.05).The Anti-Asthma Formula Ⅰ high-dose group was signifi-cantly lower than the budesonide treatment group and the Anti-Asthma Formula Ⅰ medium-and low-dose groups,with statistically significant differences(P<0.05),while there was no statistically significant difference between the Anti-Asthma Formula Ⅰ medium-and low-dose groups and the budesonide treatment group(P>0.05).Com-pared with the normal control group,HIF-1α mRNA and protein expression levels in the model control group were significantly increased,with statistically significant differences between the two groups(P<0.01).All treat-ment groups were significantly lower than the model control group,with statistically significant differences(P<0.01 or P<0.05).The Anti-Asthma Formula Ⅰ high-dose group was significantly lower than the budesonide treat-ment group and the Anti-Asthma Formula Ⅰ medium-and low-dose groups,with statistically significant differ-ences(P<0.05),while there was no statistically significant difference between the Anti-Asthma Formula Ⅰmedium-and low-dose groups and the budesonide treatment group(P>0.05).Conclusion HIF-1α plays an im-portant role in asthmatic airway remodeling.Anti-Asthma Formula Ⅰ can inhibit airway inflammation and remodel-ing and improve asthma symptoms by down-regulating HIF-1α expression.The high dose of Anti-Asthma FormulaⅠ is superior to budesonide in inhibiting HIF-1α expression and improving airway remodeling,showing potential clinical application value.

邓晨;李鹏飞;吴慧芬;林之涵

浙江中医药大学附属江南医院儿科,浙江 杭州 311201浙江中医药大学附属江南医院儿科,浙江 杭州 311201浙江中医药大学附属江南医院儿科,浙江 杭州 311201浙江中医药大学附属江南医院儿科,浙江 杭州 311201

医药卫生

支气管哮喘平喘Ⅰ号布地奈德作用机制实验研究

bronchial asthmaAnti-Asthma Formula Ⅰbudesonidemechanism of actionexperimental research

《中医儿科杂志》 2026 (2)

17-22,6

杭州市卫生计生科技计划项目(B20250169)浙江省自然科学基金项目(LY12H27011)浙江省第七批全国名老中医药专家学术经验继承项目(国中医药人教函[2022]76号).

10.16840/j.issn1673-4297.2026.02.05

评论