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Objectives：We aimed to establish ovalbumin (OVA)-induced acute and sub-acute mouse models ofasthma and evaluate effects of intranasal inhalation of various doses of OVA on airways inflammation,remodelling as well as pulmonary function measured by an invasive technique in the models proposed.
Methods：In brief, 6-8weeks female BALB/c mice were intraperitoneal injected with 100pg OVA at day 0and 12. From day 18 to 23, intranasal inhalation challenge with different doses of OVA (25} 50. 100}g}respectively) were performed to induce acute and sub-acute mouse models of asthma. At day 0. 20 (acuteperiod) and 24 (subacute period), the respiratory function parameters of excited group and control groupwere measured in single-chamber model and normal model using an invasive pulmonary function device(FIexiVent,Canada). The parameters of pulmonary mechanics were obtained after challenging withdifferent concentrations of methacholine. After collecting bronchoalveolar lavage (BAL) fluid of eachgroup the cells were counted with hematoxylin/eosin (H&E) or Congo red staining. H&E, Periodicacid-Schiff (PAS) and Masson stainings were employed to paraffin- embedded sections derived from the left lungs to identi句inflammatory cell infiltration, mucus expression and other airway remodelingindicators.
Results： At day of 20, 24, the airway responsiveness of 50 and 100ug OVA-challenged groups wassignificantly higher than those of 25pg OVA-challenged group, while there was no significant differencebetween 25ug OVA-challenged group and saline control group. Compared with saline group, the counts of BAL cells in 50 and 100ug OVA-challenged groups were significantly increased. Adding to these, theproportion of BAL inflammatory cells (neutrophils, eosinophils and mononuclear cells) also significantlyelevated. Compared with 50 and 1001.ig groups, cellular counts of BALF leukocytes of 25pg OVA-challenged group were mildly increased, including eosinophils. The HE stained paraffin-embeddedlung sections of 100 and 50pg OVA-challenged groups showed there were large amounts of inflammatorycells around the alveolar, bronchial wall, bronchial lumen and blood vessels. Bronchial mucosa was alsoincreasingly extended and thickened. A great amount of mucous sputum plugs existed in the bronchiallumens. Congo red staining of lung sections of 100 and 50pg OVA-challenged groups showed that a largenumber of eosinophils infiltrated in the bronchial and blood vessels. However, the infiltration ofeosinophil was not markedly observed in 25pg OVA-challenged group and saline group.
Conclusion：Here we reported that we successfully established acute and sub-acute mouse models ofasthma. Intranasal challenge with different doses of OVA induces varying degrees of changes in airways inflammation, remodelling and pulmonary functions in mouse models of asthma. Our studies providedthe foundation for further research on the pathogenesis of asthma and drug screening in mouse asthmamodels.
Methods：In brief, 6-8weeks female BALB/c mice were intraperitoneal injected with 100pg OVA at day 0and 12. From day 18 to 23, intranasal inhalation challenge with different doses of OVA (25} 50. 100}g}respectively) were performed to induce acute and sub-acute mouse models of asthma. At day 0. 20 (acuteperiod) and 24 (subacute period), the respiratory function parameters of excited group and control groupwere measured in single-chamber model and normal model using an invasive pulmonary function device(FIexiVent,Canada). The parameters of pulmonary mechanics were obtained after challenging withdifferent concentrations of methacholine. After collecting bronchoalveolar lavage (BAL) fluid of eachgroup the cells were counted with hematoxylin/eosin (H&E) or Congo red staining. H&E, Periodicacid-Schiff (PAS) and Masson stainings were employed to paraffin- embedded sections derived from the left lungs to identi句inflammatory cell infiltration, mucus expression and other airway remodelingindicators.
Results： At day of 20, 24, the airway responsiveness of 50 and 100ug OVA-challenged groups wassignificantly higher than those of 25pg OVA-challenged group, while there was no significant differencebetween 25ug OVA-challenged group and saline control group. Compared with saline group, the counts of BAL cells in 50 and 100ug OVA-challenged groups were significantly increased. Adding to these, theproportion of BAL inflammatory cells (neutrophils, eosinophils and mononuclear cells) also significantlyelevated. Compared with 50 and 1001.ig groups, cellular counts of BALF leukocytes of 25pg OVA-challenged group were mildly increased, including eosinophils. The HE stained paraffin-embeddedlung sections of 100 and 50pg OVA-challenged groups showed there were large amounts of inflammatorycells around the alveolar, bronchial wall, bronchial lumen and blood vessels. Bronchial mucosa was alsoincreasingly extended and thickened. A great amount of mucous sputum plugs existed in the bronchiallumens. Congo red staining of lung sections of 100 and 50pg OVA-challenged groups showed that a largenumber of eosinophils infiltrated in the bronchial and blood vessels. However, the infiltration ofeosinophil was not markedly observed in 25pg OVA-challenged group and saline group.
Conclusion：Here we reported that we successfully established acute and sub-acute mouse models ofasthma. Intranasal challenge with different doses of OVA induces varying degrees of changes in airways inflammation, remodelling and pulmonary functions in mouse models of asthma. Our studies providedthe foundation for further research on the pathogenesis of asthma and drug screening in mouse asthmamodels.