三氧化二砷对实验性小鼠支气管哮喘气道重塑及TGF-β1、VEGF表达的影响

摘要

Objective To investigate the effects of arsenic trioxide ( As2 O3 ) on preventing airway remodeling in bronchial asthma. Methods Forty BALB/c mice were randomly assigned to 4 groups: normal control group ( sterile saline only) , model group, dexamethasone (DXM) and As2O3 treatment groups. Mice were sensitized by intraperitoneal injection with 10% ovalbamin(OVA) for 2 weeks prior to OVA inhalation challenge. OVA challenges were for 8 weeks. After OVA challenge, typical chronic asthma-like morphology changes were observed in the bronchi and lung tissues in model group. The indicators of airway remodeling was measured by image analysis system, the transforming growth factor p, (TGF-p, ) and vascular endothelial growth factor (VEGF) protein expression were measured immunohistochemically,and the levels of TGF-p, and VEGF mRNA were measured by RT-PCR. Results The changes in lung tissues in the DXM and As2O3 groups were compared with those of the model group, but showing no significant differences between the DXM and As2O3 groups. TGF-p, and VEGF expressions were significantly enhanced in lung tissues of mice in model group. However, TGF-p, and VEGF protein levels and mRNA expressions were significantly decreased in As2O3 or DXM treatment groups and airway remodeling was significantly ameliorated. Conclusion The results suggest that 8-week OVA challenges after sensitization produce allergens, stimulating the airway remodeling in asthma model, DXM and As2O3 inhibit airway remodeling in chronic asthma and their mechanisms may be related to inhibiting the expressions of TGF-p, and VEGF.%目的 探讨三氧化二砷( As2O3)对支气管哮喘气道重塑的影响.方法 将实验BALB/c小鼠40只随机分为正常对照组、模型组、地塞米松治疗组和As2O3治疗组,模型组通过腹腔注射卵白蛋白(OVA)致敏及反复雾化OVA吸入激发8周,建立支气管哮喘气道重塑动物模型,地塞米松和As2O3治疗组每次雾化吸入前分别给予地塞米松2 mg/kg和As2O34 mg/kg腹腔内注射.应用HE染色,观察支气管、肺组织的病理形态改变,应用图像分析系统测定气道重塑指标,应用免疫组化法检测各组小鼠肺组织中的转化生长因子p1(TGF-β1)、血管内皮生长因子(VEGF)的蛋白表达,应用逆转录-聚合酶链反应(RT-PCR)法检测各组肺组织中的TGF-β1和VEGF mRNA表达水平.结果 模型组小鼠经过8周过敏原激发后,肺组织病理学发生了较典型的哮喘样改变；地塞米松组和As2O3组小鼠的肺部组织病理学改变较模型组为轻,两组之间无显著差异.模型组小鼠肺组织中TGF-β1、VEGF的蛋白和mRNA表达均增强；与模型组相比,地塞米松组和As2O3组肺组织中TGF-β1、VEGF的蛋白和mRNA的表达均较弱,但仍强于正常对照组.结论 致敏后给予8周过敏原激发可成功建立小鼠哮喘气道重塑模型；地塞米松和As2O3治疗均可抑制哮喘的气道重塑过程,其作用机制可能与抑制TGF-β1、VEGF的表达有关.