Prolonged allergen exposure induces structural airway changes in sensitized rats
Prolonged allergen exposure induces structural airway changes in sensitized rats
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DOI：
10.1164/ajrccm.161.2.9902094
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发表时间：
2000-02-01
影响因子：
24.7
通讯作者：
Pauwels, RA
中科院分区：
文献类型：
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作者：
Palmans, E;Kips, JC;Pauwels, RA
哮喘气道重塑的发病机制和功能后果仍有待完全确定。在本研究中，我们评估了长期接触过敏原对大鼠气道功能和结构的影响。致敏的棕色挪威大鼠反复暴露于雾化卵清蛋白（OA）或磷酸盐缓冲盐水（PBS）2-4或12周。 OA 暴露导致 OA 特异性血清 IgE 和支气管周围嗜酸性粒细胞数量持续增加。 OA暴露2周后，气道组织学显示杯状细胞增生、气道上皮中溴脱氧尿苷阳性细胞增加、纤连蛋白沉积增加以及气道内壁区域增厚。这与雾化卡巴胆碱的气道高反应性（AHR）同时发生。 OA 暴露 12 周后，在粘膜下层观察到纤连蛋白（与 PBS 相比，p < 0.05）和胶原沉积（与 PBS 相比，p < 0.05）增加。暴露 12 周后，总壁面积、内壁面积或气道对卡巴胆碱的反应性与 PBS 暴露的动物不再有显着差异。总之，大鼠长期暴露于 OA 会引起气道结构变化，与哮喘气道重塑相似。研究数据进一步表明，根据重塑的程度和分布，细胞外基质的变化可以增强或预防 AHR。
The pathogenesis and functional consequences of airway remodeling in asthma remain to be fully established. In the present study we evaluated the effect of prolonged allergen exposure on airway function and structure in rats. Sensitized Brown Norway rats were repeatedly exposed for periods of 2 4, or 12 wk to aerosolized ovalbumin (OA) or phosphate-buffered saline (PBS). OA exposure induced a persistent increase in OA-specific serum IgE and in the number of peribronchial eosinophils. After 2 wk of OA exposure, airway histology revealed goblet-cell hyperplasia, an increase in bromodeoxyuridine-positive cells in airway epithelium, increased fibronectin deposition, and a thickening of the airway inner wall area. This coincided with airway hyperresponsiveness (AHR) to aerosolized carbachol. After OA exposure for 12 wk, increased fibronectin (p < 0.05 versus PBS) and collagen deposition (p < 0.05 versus PBS) were observed in the submucosa. After 12 wk of exposure, neither total nor inner wall area or airway responsiveness to carbachol were any longer significantly different from those of PBS-exposed animals. In conclusion, prolonged OA exposure in rats induces structural airway changes that bear similarities to airway remodeling in asthma. The study data further indicate that depending on the extent and distribution of remodeling, changes in the extracellular matrix can enhance or protect against AHR.