哮喘气道重塑小鼠模型的构建及病理学特征变化的探讨

Establishment of mouse model of asthma airway remodeling and investigation of pathological features

目的构建哮喘气道重塑小鼠模型并观察不同雾化吸入激发时间气道重塑病理学特征的变化。方法采用卵蛋白(ovalbumin,OVA)腹腔致敏小鼠,1%OVA雾化吸入激发小鼠,末次激发24 h后处死小鼠以构建致敏小鼠模型。模型组依据雾化吸入激发时间不同,分为2、4、6、8周和10周5组。收集支气管肺泡灌洗液(bronchoveolar lavage fluid,BALF)分类计数嗜酸性粒细胞总数,肺组织切片HE、PAS、Masson观察病理变化。结果与正常组相比,各激发时长的模型组细胞总数和嗜酸性粒细胞总数均明显增高(P≤0.001),嗜酸性粒细胞浸润,杯状细胞化生均明显加重(P<0.001),但是气道基底膜仅在8周和10周组增厚明显(P≤0.036)。结论气道重塑开始于炎症早期,随着激发时间推移而逐渐加重,但各项气道重塑特征呈现的时间段不一致,气道重塑病理特征的形成需约8周的时间激发才能完整呈现。

Objective To establish a mouse model of asthma airway remodeling and investigate the changes of pathological features at different challenging time. Methods The mice were randomly divided into1 control group and 5 model groups（ 2-,4-,6-,8- and 10-week groups） according to different challenging time. To make the airway remodeling in the allergic mice,the mice were sensitized with ovalbumin（ OVA）and repeatedly challenged with OVA. Bronchoalveolar lavage fluids（ BALF） were collected for counting total cells and eosinophils（ EOS） at 24 h after the last challenge. The pathological changes of lung tissues were observed by HE,PAS and Masson staining. Results Compared with the control group,the counts of total cells and EOS were increased（ P≤0. 001）,and the scores of EOS infiltration and goblet cell hyperplasia were significantly higher in the 5 model groups（ P〈 0. 001）. However,the airway basement membrane was thicker only in the 8-week group and 10-week group（ P ≤0. 036）. Conclusion Airway remodeling begins in the early stage of inflammation and becomes more serious along with the challenge time. However,the pathological characteristics of remodeling do not appear at the same time. The challenge of about 8 weeks is necessary to exhibit complete pathological characteristics of airway remodeling.