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雾化聚合 I 型胶原蛋白可减少变应性哮喘豚鼠模型的气道炎症和重塑。

Aerosolized polymerized type I collagen reduces airway inflammation and remodelling in a guinea pig model of allergic asthma.

机构信息

Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Insurgentes Sur 3700, CP 04510 Mexico, DF, Mexico.

出版信息

Lung. 2010 Apr;188(2):97-105. doi: 10.1007/s00408-009-9202-2. Epub 2009 Dec 9.

Abstract

Collagen-polyvinylpyrrolidone (Collagen-PVP) has been demonstrated to elicit immunomodulatory properties in different chronic inflammatory diseases. Nevertheless, its effects on asthma are still unknown. We have evaluated whether collagen-PVP could modulate airway inflammation and remodelling in a guinea pig model of allergic asthma. Sensitized guinea pigs were challenged with the allergen (ovalbumin) six times (at 10-day intervals). From the third challenge on, animals were treated every 5 days with saline aerosols containing 0.16, 0.33, or 0.66 mg/ml of collagen-PVP (n = 5, respectively). Some guinea pigs, sensitized and challenged with saline as well as treated with 0 or 0.66 mg/ml collagen-PVP, were included in the study as control (n = 7) and sham groups (n = 5), respectively. From the first challenge on, ovalbumin induced a transient airway obstruction, measured by barometric plethysmography, which was not modified by collagen-PVP treatments. After the last allergen challenge, guinea pigs were anesthetized to obtain bronchoalveolar lavage (BAL) and the left lung caudal lobe. As expected, BAL cell count from allergen-challenged guinea pigs showed abundant neutrophils and eosinophils, as well as numerous tumor necrosis factor (TNF)-alpha-expressing granulocytes and macrophages in airway wall (determined by immunohistochemical assay). Neutrophilia and TNF-alpha-expressing leukocytes, from collagen-PVP treated animals, diminished from 0.16 mg/ml, and eosinophilia from 0.66 mg/ml of collagen-PVP doses. Histological changes induced by allergen challenges include thickening of connective tissue below airway epithelium and vascular wall widening of airway adjacent vessels; these changes were reduced by collagen-PVP treatment. Collagen-PVP seems to have anti-inflammatory and antifibrotic properties in this guinea pig asthma model.

摘要

胶原蛋白-聚乙烯吡咯烷酮(Collagen-PVP)已被证明在不同的慢性炎症性疾病中具有免疫调节作用。然而,其在哮喘中的作用尚不清楚。我们评估了胶原蛋白-PVP 是否可以调节变应性哮喘豚鼠模型中的气道炎症和重塑。致敏豚鼠用过敏原(卵清蛋白)进行了 6 次挑战(间隔 10 天)。从第三次挑战开始,动物每隔 5 天用含有 0.16、0.33 或 0.66 mg/ml 胶原蛋白-PVP 的生理盐水气雾剂处理(分别为 n = 5)。一些致敏并用生理盐水挑战以及用 0 或 0.66 mg/ml 胶原蛋白-PVP 治疗的豚鼠作为对照(n = 7)和假手术组(n = 5)分别纳入研究。从第一次挑战开始,气道阻力的测量表明,胶原蛋白-PVP 处理并未改变卵清蛋白诱导的短暂气道阻塞。最后一次过敏原挑战后,豚鼠被麻醉以获得支气管肺泡灌洗(BAL)和左肺尾叶。正如预期的那样,来自过敏原挑战豚鼠的 BAL 细胞计数显示大量中性粒细胞和嗜酸性粒细胞,以及气道壁中大量表达肿瘤坏死因子(TNF)-α的粒细胞和巨噬细胞(通过免疫组织化学测定确定)。来自胶原蛋白-PVP 处理动物的中性粒细胞增多和表达 TNF-α的白细胞从 0.16 mg/ml 减少,并且从 0.66 mg/ml 的胶原蛋白-PVP 剂量减少嗜酸性粒细胞增多。过敏原挑战引起的组织学变化包括气道上皮下结缔组织增厚和相邻气道血管壁变宽;胶原蛋白-PVP 处理可减轻这些变化。胶原蛋白-PVP 在这种豚鼠哮喘模型中似乎具有抗炎和抗纤维化作用。

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