摘要
目的观察布地奈德对反复暴露于变应原的致敏豚鼠气道变应性炎症和细胞外基质沉积的影响。方法雄性Hartley系豚鼠共32只,分为4组。A组:反复卵白蛋白(OVA)暴露组;B组:反复OVA暴露+布地奈德(BUD)干预组;C组:中断OVA暴露+中断BUD干预组;D组:正常对照组。实验8周时对各组支气管肺泡灌洗液行细胞分类计数及肺组织切片气道嗜酸细胞计数,免疫组织化学染色检测并定量分析气道壁沉积的纤维黏连蛋白和Ⅲ型胶原。结果(1)支气管肺泡灌洗液嗜酸细胞数:A组、B组高于C组和D组(P<0·01),且A与B,B与C间差异有统计学意义。(2)各级气道壁浸润的嗜酸细胞:A、B组高于C、D组,且中小气道A与B,B与C间差异有统计学意义。(3)中小气道纤维黏连蛋白灰度值:A组(中气道122±22,小气道135±29)、B组(中气道174±23,小气道165±41)低于C组(中气道219±34,小气道236±20)和D组(中气道229±20,小气道220±16)(P均<0·05),A与B,B与C间差异有统计学意义。(4)中小气道Ⅲ型胶原灰度值:A组(中气道153±21,小气道133±23)、B组(中气道174±22,小气道176±20)低于C组(中气道189±14,小气道191±14)、D组(中气道200±18,小气道198±20)(P均<0.05),且A与B间差异有统计学意义。结论在反复暴露于OVA的情况下持续BUD干预仅能部分抑制豚鼠慢性哮喘模型的气道变应性炎症和细胞外基质沉积,而早期BUD干预并中断OVA暴露可能完全抑制这类变化。
Objective Inhaled glucocorticosteroids (ICS) remains the first line controller medication for chronic airway inflammation in asthma till now. If the impact of allergen could not be eliminated, how would the improvement of airway inflammation be achieved with inhaled glucocorticosteroids therapy? What was its effect on airway remodeling? In this study, an animal model of asthma was established and the effects of budesonide on airway allergic inflammation and extracellular matrix (ECM) deposition in sensitized guinea pigs with repeated exposure to allergen were investigated. Methods Thirty-two male Hartley guinea pigs were randomly divided into four groups with 8 in each group:(A) Group of repeated exposure to ovalbumin (OVA), (B) Group of repeated exposure to OVA plus budesonide (BUD) intervention, (C) Group of stopping repeated exposure to OVA plus stopping BUD intervention, (D) Control group. At 24 h after the last OVA challenge (8 weeks after the first OVA challenge), bronchoalveolar lavage fluid (BALF) was collected from each animal. Total and differential leukocyte counts in BALF was performed on cell suspension smear stained with May-Grünwald-Giemsa (MGG) method. The upper lobe of right lung was removed and regularly fixed, then paraffin embedded lung tissues sections were prepared. The count of eosinophils infiltrated in the airway wall was performed on H&E stained lung tissue sections with LEICA Q500IW computerized image analysis system. Fibronectin and collagen type Ⅲ(Col-Ⅲ) deposited in the airway wall were detected by immunohistochemical staining on the paraffin embedded lung tissues sections. The intensity of positive reaction of fibronectin or Col-Ⅲ deposited in the airway wall was analyzed with LEICA Q500IW computerized image analysis system. Results The count of eosinophils in BALF(×10 5/ml)of group A and B were higher than that of group C and D (35.70±25.22, 11.49±5.51 vs. 1.00±0.90, 1.02±0.78, P <0.01), the difference between group A and B, group B and C was significant. The count of eosinophils infiltrated at each level of airway wall in group A and B were higher than that of group C and D (large airway: 6.95±2.28, 1.54±1.09 vs. 0.76±0.45, 0.88±0.25;medial airway: 9.22±3.89, 3.99±2.3 vs. 1.25±1.20, 0.64±0.36;small airway: 11.56±4.02, 2.67± 1.15 vs. 1.32±0.83, 0.43±0.24, P <0.01), the difference between group A and B, group B and C was significant. The gray values of fibronectin deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 122±22, 174±23 vs. 219±34, 229±20;small airway 135±29, 165±41 vs. 236±20, 220±16, P <0.05), the difference between group A and B, group B and C was significant. The gray values of Col-Ⅲ deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 153±21, 174±22 vs. 189±14, 200±18;small airway 133±23, 176±20 vs. 191±14, 198±20, P <0.05), the difference between group A and B was significant. Conclusion Inhaled budesonide could partially inhibit allergic inflammation and ECM deposition in airway wall in guinea pig chronic asthma model with repeated exposure to allergen. Early inhaled budesonide combined with avoidance of OVA exposure could completely inhibit allergic inflammation and ECM deposition. These results suggest that the inhibitory effect on airway allergic inflammation and airway remodeling of inhaled glucocorticosteroids would be limited when the allergen factor could not be avoided.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2005年第6期414-417,共4页
Chinese Journal of Pediatrics
