VEGF Ang-1与支气管哮喘气道重塑的关系

目的制备慢性支气管哮喘（简称哮喘）小鼠模型以观察VEGF、Ang-1的改变及其与气道血管生成的关系,初步探讨气道血管生成机制及在气道重塑中的意义。方法BALB-c小鼠随机数字表分为正常对照组（A组）、慢性哮喘组（B组）、地塞米松治疗组（C组）,每组10只,采用腹腔注射OVA致敏,长期吸入OVA悬液激发制备模型。A组以生理盐水代替OVA,C组每次激发前地塞米松腹腔注射干预。末次激发后24h内处死,随即行右肺盥洗留取BALF,左肺及气管固定、包埋制备病理切片,行HE染色和抗VEGF、Ang-1免疫组化染色,观察气道形态学改变。ELISA法检测BALF中VEGF的浓度。结果气道血管密度、WAt/Pbm、BALF中VEGF浓度B组明显高于A组（P均〈0.01）,C组低于B组（P均〈0.01）,高于A组（P均〈0.05）;气道血管密度与WAt/Pbm、VEGF的浓度呈正相关。结论慢性哮喘小鼠模型气道血管生长在气道重塑中具有重要意义,气道血管生长可能与气道血管生长因子失调有关,糖皮质激素能部分抑制气道血管生长,进而改善慢性哮喘气道结构的重塑。

Relation between vascular endothelial growth factor and angiopoietin 1 and the airway remodeling of asthma

Objective To observe the changes of VEGF and Ang-1 and their relations with the airway Anglogenesis in a chronic asthmatic mouse model,elucidate the airway Angiogenesis mechanisms and influence on the airway remodeling. Methods Thirty BALB-c mice were randomly divided into three groups randomly：normal control group （A）, chronic asthmatic group （B）,dexamethasone treated chronic asthmatic group （C）.We developed a chronic asthmatic mouse model by repeatedly sensitized to allergen（ OVA ） intraperitoneally in which chronic airway inflammation was maintained by repeatedly challenged with OVA.Mice in A group were sensitized and challenged with equal volume of NS on the same days.Mice in C received 2 mg/kg dexamethasone intraperitoneally lh before each challeng respectively. Twenty-four hours after the last challenge the mice were killed.Right lungs were lavaged and bronchoalveolar lavage fluid （ BALF ） were reserved.Left lungs and tracheae were fixed with 10% bufferedformalin and embedded in paraffin in 24h. Pathological slides were made from left lungs and tracheae and stained with hematoxylin-eosin,immunohistochemisry was employed to observe the expression and localization of VEGF and Ang-1.Results The density of vessels in tracheal lamina propria and submucosa,The airway wall hasement membrane perimeter/total hronchial wall area （ WAt/Pbm ）,The concentration of VEGF and Ang-1 in BALF B group was higher than that in A group （P average〈0.01 ）;C group was lower than B group （ P average〈 0.01 ）;C group higher than A group （ P average〈0.05 ）.There was a significant positive correlation between the density of vessels with WAt/Pbm and The concentration of VEGF in BALF.Conclusion Airway angiogenesis in the chronic asthmatic mice had significantly influence on the airway remodeling.The airway angiogenesis might be the result of the excessive proliferation of angiogenic factors in the chronic asthmatic airway. Glucocorticoid can inhibit VEGF proliferation partly and attenuate the air