布地奈德对慢性支气管哮喘小鼠肺组织HIF-1α和VEGF表达及气道重塑的影响

Effects of budesonide on HIF-1α and VEGF expression and airway remodeling in an asthmatic mouse model

摘要:

目的：研究布地奈德对慢性哮喘小鼠缺氧诱导因子-1α（HIF-1α）、血管内皮生长因子(VEGF)表达的调控和对血管生成、气道重塑的影响。方法：30只雌性BALB/c小鼠随机分为对照组、模型组和治疗组，每组10只。卵清蛋白（OVA）激发试验建立哮喘小鼠模型，治疗组从第28天开始每日在OVA激发前1 h雾化吸入布地奈德100 μg/kg，对照组以PBS代替OVA。苏木精-伊红染色分析气管管壁厚度变化，Masson染色分析肺组织胶原沉积，免疫组织化学染色法检测肺组织血管生成情况，免疫组织化学染色法和Western blot检测HIF-1α、VEGF表达水平。分析气管管壁厚度、血管面积百分比与VEGF、HIF-1α表达的相关性。结果：模型组较对照组气道管壁增厚，肺组织胶原沉积、血管面积、HIF-1α和VEGF表达显著增加；治疗组较模型组气道管壁厚度、肺组织胶原沉积及血管面积减少，HIF-1α和VEGF表达显著下降。气道管壁厚度、血管面积分别与HIF-1α及VEGF表达呈正相关，HIF-1α与VEGF表达亦呈正相关。结论：布地奈德通过抑制HIF-1α、VEGF表达，明显减轻哮喘小鼠肺组织血管生成和气道重塑。

Abstract:

OBJECTIVE: To study the effects of budesonide on hypoxia inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) expression, angiogenesis and airway remodeling in the chronic asthmatic mouse model. METHODS: Thirty female BALB/c mice were randomly divided into normal control, asthma model and treatment groups (10 in each group).The asthmatic mouse model was established via OVA challenge test. Mice in the treatment group were administered with aerosol budesonide (100 μg/kg) an hour before the OVA challenge test from the 28th day. Mice in the control group were treated with PBS instead of OVA. Hematoxylin and eosin staining was performed to observe thickness of the airway wall. Masson staining was used for examing collagen deposition of lung tissues. Angiogenesis and HIF-1α and VEGF expression were measured using immunohistochemistry and Western blot. The relationship of airway wall thickness and vessel area to HIF-1α and VEGF expression was investigated. RESULTS: Vessel area, collagen deposition of lung tissues and airway wall thickness increased in the asthma model group. Levels of HIF-1α and VEGF were also elevated. Administration of budesonide significantly reduced angiogenesis, collagen deposition of lung tissues and airway wall thickening, as well as expression of HIF-1α and VEGF. The vessel area and airway wall thickness were positively correlated with expression of HIF-1α and VEGF. A positive correlation was also found between the expression of HIF-1α and VEGF. CONCLUSIONS: Budesonide can decease angiogenesis and airway remodeling by inhibiting HIF-1α and VEGF expression in asthmatic mice.