关键词:哮喘,小鼠模型,激发时间,气道炎症,气道重塑

Abstract:Objective：To establish an asthmatic mouse model with different challenging times，to evaluate the effects of different challenging time on murine asthmatic airway inflammation，airway remodeling and the level of interleukin-17 （IL-17）.Methods：Ovalbumin（OVA） was used as an allergen to sensitize and challenge the murines. Forty-eight female specific-free （SPF） BALB/c mice aged four weeks were randomly divided into 6 groups according to challenging time length：3 days group，6 days group，12 days group，and each set of normal control group. Mice were sacrificed after the last 24 hours allergen challenge. Bronchoalveolar lavage fluid （BALF） was collected for leukocytes count analysis. IL-17 levels in BALF supernatant were analyzed by enzyme-linked immunosorbent assay （ELISA）. For histopathological examination，HE staining was used to measure the infiltration of inflammatory cells，AB-PAS was used to measure the hyperplasia of goblet cells and mucin，Masson staining was used to measure collagen deposition. Goblet cell area （Wag），smooth muscle area （Wam）， collagen area （Wcol），and the perimeter of bronchial basemen membrane （Pbm） were recorded.Results：4 weeks mice can appear typical asthma airway inflammation reaction after 3 days’ challenge，the inflammation scores and inflammatory markers such as total number of leukocytes were significant elevated compared with controls （P?0.01）. 6 days challenging time later， the inflammation scores and inflammatory markers continued to increase compared with 3 challenging days group （P<0.01）. For 12 challenging days group，the inflammation scores and the percentage of eosinophils were elevated compared with 3 challenging days group （P<0.01）， but there were no statistically significant differences between 12 challenging days group and 6 challenging days group （P>0.05）. The percentage of neutrophils and the staining area of goblet cells in the 3 groups were increased in turn significant （P<0.01）. Collagen deposition around the airway and the increase of airway smooth muscle mass can be observed after 6 days’ challenge， the hyperplasia degree were significant increased after 12 days’ challenging （P<0.01）. The levels of IL-17 in the 3 groups were elevated in turn significant （P<0.01）.Conclusions：The characteristics and pathogenesis of asthma have certain heterogeneity，different challenging time may lead to different pathological asthmatic phenotypes. It is necessary to select reasonable challenging time according to different research purpose when we prepare asthma models.

Key words:asthma,mouse modelchallenging time,airway inflammation,airway ,remodeling