[实验性哮喘气道炎症和重塑小鼠模型的建立]

[Development of a murine model of airway inflammation and remodeling in experimental asthma].

作者信息

Fraga-Iriso Rebeca, Núñez-Naveira Laura, Brienza Nadia S, Centeno-Cortés Alberto, López-Peláez Eduardo, Verea Héctor, Ramos-Barbón David

机构信息

Unidad de Investigación Respiratoria, Servicio de Neumología, Complejo Hospitalario Universitario, Instituto de Investigación Biomédica de A Coruña (INIBIC), A Coruña, España.

出版信息

Arch Bronconeumol. 2009 Sep;45(9):422-8. doi: 10.1016/j.arbres.2009.01.014. Epub 2009 May 21.

DOI:10.1016/j.arbres.2009.01.014

PMID:19464098

Abstract

BACKGROUND AND OBJECTIVE

Experimental animal models are necessary for studying asthma disease mechanisms and for identifying new therapeutic targets. We present a murine model of experimental asthma that allows integrated, quantitative assessment of airway inflammation and remodeling.

MATERIAL AND METHODS

BALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA or vehicle 3 times per week for 12 weeks.

RESULTS

On bronchoalveolar lavage, the OVA-sensitized mice had significantly higher total leukocyte counts, with a median (Q25-Q75) of 670.0 cells/mL x 10(3) (376.2, 952.5) in comparison with 40.0 cells/mL x 10(3) (60.0-85.0) in controls (P=.001), and higher eosinophil and differential lymphocyte counts. In sagittal sections of lungs inflated to a standard pressure, the OVA-sensitized animals showed goblet cell hyperplasia in the respiratory epithelium (periodic acid-Schiff staining, 53.89 [36.26-62.84]cells/mm(2) vs 0.66 [0.00-1.06]cells/mm(2), P<.001), dense mononuclear and eosinophilic inflammatory infiltrates (hematoxylin-eosin, 32.87 [27.34-37.13]eosinophils/mm(2) vs 0.06 [0.00-0.20]eosinophils/mm(2), P=.002), subepithelial infiltration by mast cells (toluidine blue, 2.88 [2.00-3.28] mast cells/mm(2) vs 0.28 [0.15-0.35] mast cells/mm(2), P<.001), increased contractile tissue mass (immunofluorescence analysis for alpha-smooth-muscle actin, 2.60 [2.28-2.98] vs 1.08 [0.93-1.16], dimensionless, P<.001) and enhanced extracellular matrix deposition (Masson's trichrome, 2.18 [1.85-2.80] vs 0.50 [0.37-0.65], dimensionless, P<.001).

CONCLUSIONS

Our dataset describes an experimental model of asthma which is driven by prolonged allergen exposure and in which airway inflammation and remodeling develop and are assessed together.

摘要

背景与目的

实验动物模型对于研究哮喘疾病机制及确定新的治疗靶点十分必要。我们提出一种实验性哮喘小鼠模型，该模型能够对气道炎症和重塑进行综合、定量评估。

材料与方法

将BALB/c小鼠用卵清蛋白（OVA）致敏，并每周用OVA或赋形剂攻击3次，持续12周。

结果

支气管肺泡灌洗显示，OVA致敏小鼠的总白细胞计数显著更高，中位数（第25 - 75百分位数）为670.0个细胞/mL×10³（376.2，952.5），而对照组为40.0个细胞/mL×10³（60.0 - 85.0）（P = 0.001），且嗜酸性粒细胞和淋巴细胞分类计数更高。在充气至标准压力的肺矢状切片中，OVA致敏动物的呼吸上皮出现杯状细胞增生（过碘酸 - 希夫染色，53.89 [36.26 - 62.84]个细胞/mm² 对比 0.66 [0.00 - 1.06]个细胞/mm²，P < 0.001），有密集的单核和嗜酸性炎症浸润（苏木精 - 伊红染色，32.87 [27.34 - 37.13]个嗜酸性粒细胞/mm² 对比 0.06 [0.00 - 0.20]个嗜酸性粒细胞/mm²，P = 0.002），肥大细胞在基底膜下浸润（甲苯胺蓝染色，2.88 [2.00 - 3.28]个肥大细胞/mm² 对比 0.28 [0.15 - 0.35]个肥大细胞/mm²，P < 0.001），收缩组织质量增加（α - 平滑肌肌动蛋白免疫荧光分析，2.60 [2.28 - 2.98] 对比 1.08 [0.93 - 1.16]，无量纲，P < 0.001）以及细胞外基质沉积增强（Masson三色染色，2.18 [1.85 - 2.80] 对比 0.50 [0.37 - 0.65]，无量纲，P < 0.001）。