吸入氟替卡松对哮喘患者气道血管生成及血管内皮生长因子的影响
2007/06/27
近年研究发现，气道上皮下血管分布增加及血管生成增多是导致哮喘气道重塑的重要因素之一。尽管糖皮质激素在缓解气道炎症、改善肺功能中的疗效得到肯定，但尚不清楚吸入糖皮质激素对哮喘患者气道血管分布及血管生成的影响。2007年4月发表于Thorax上的一篇研究报道了吸入氟替卡松对哮喘患者气道血管分布、血管内皮生长因子（VEGF）及其受体和血管生成素的影响。研究者采用安慰剂对照方法，检测了35个哮喘患者激发（3～4周）前后气道黏膜活检标本、支气管肺泡灌洗液中相关指标，结果发现，吸入氟替卡松3个月后，哮喘患者气道血管分布、VEGF表达及血管芽显著减少。该研究认为，吸入糖皮质激素通过下调VEGF活性，抑制了因血管生成增多导致的气道重塑。
（毛辉 成都，四川大学华西医院呼吸科 610041 摘译）
Effects of inhaled fluticasone on angiogenesis and vascular endothelial growth factor in asthma
B N Feltis1, D Wignarajah2, D W Reid1, C Ward3, R Harding4 and E H Walters1
Background: Subepithelial hypervascularity and angiogenesis in the airways are part of structural remodelling of the airway wall in asthma, but the effects of inhaled corticosteroids (ICS) on these have not been explored. Increased vascularity in asthma may contribute to a number of functional abnormalities. A study was undertaken to explore angiogenic modulation by ICS and its likely regulation via vascular endothelial growth factor (VEGF), its receptors and the angiopoietins.
Methods: A placebo-controlled intervention study with ICS in asthma was performed, examining vascularity, VEGF, its receptors (VEGFR1 and VEGFR2), and angiopoietin-1 (Ang1) to assess which of these factors were changed in the asthmatic airways after ICS treatment. Airway wall biopsy specimens, lavage fluid and cells were obtained from 35 patients with mild asthma randomised to receive ICS or placebo for 3 months, after which bronchoscopic examination and sample collection were repeated. Immunohistochemistry and image analysis were used to obtain quantitative measures of vessels, angiogenic sprouts, VEGF, VEGFR1, VEGFR2 and Ang1 staining in airway biopsy specimens. ELISA was used to assess VEGF concentrations in the lavage fluid.
Results: Vessel, VEGF and sprout staining were decreased after 3 months of ICS treatment. VEGF levels remained unchanged. VEGF receptors and Ang1 staining were not reduced after treatment.
Conclusions: The findings of this study support an effect of ICS in downregulating angiogenic remodelling in the airways in asthma, associated with decreasing VEGF activity within the airway wall. The environment of the airways after treatment with ICS, with changes in the balance between VEGF, its receptors, Ang1 and sprouts, appears to be less angiogenic than in untreated asthma.
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抗原激发后的哮喘气道高反应性与气道重塑相关而非持续气道炎症
