| Effects of neonatal hyperoxia on ovalbumin-induced asthma model in adult miceObjective This study aims to investigate the effect of neonatal hyperoxia exposure on female ovalbumin(OVA)-induced asthma model in mice.Methods 32 female BALB/c mice pups were randomly assigned to four groups: Room air-PBS group,Hyperoxia-PBS group,Room air-OVA group and HyperoxiaOVA group,with 8 mice in each group.Mice in Hyperoxia-PBS group and HyperoxiaOVA group were exposed to hyperoxia(Fi O2 ? 95%)for 7 days,meanwhile mice in Room air-PBS group and Room air-OVA group were raised in room air(Fi O2 = 21%).After 7 days,the Hyperoxia-PBS group and Hyperoxia-OVA group were removed from hyperoxia and raised the same environment with the Room air-PBS group and the Room air-OVA group.Mice in Room air-OVA group and Hyperoxia-OVA group were given intraperitoneal injection of sensitization suspension [OVA 1mg/ml+Al(OH)3] from the age of 65 days.All the animals were sacrificed for bronchoalveolar lavage,and the bronchoalveolar lavage fluid(BALF)was collected for leukocyte counting.The levels of IL-5,IL-12,IL-13 in BALF and Ig E in serum were detected by ELISA.The lung tissue of mice in each group was analysis by histological staining for pathological changes.Results Compared with Room air-OVA group,the level of serum in Ig E of Hyperoxia-OVA group was significantly higher(15.63 3.57 vs 11.85 2.89,P < 0.05),the number of eosinophils in BALF was increased(66.19 14.51 vs 40.85 8.07,P < 0.05),the number of lymphocytes was increased(30.64 10.57 vs 10.36 2.56,P < 0.05),the number of monocytes was increased(4.62 1.77 vs 1.71 0.27,P < 0.05),and the level of IL-5 was increased(114.91 18.84 vs 0.01,P<0.05),with IL-12 decreased(173.47 111.75 vs 74.94 48.86,P < 0.01)and IL-13 increased(24.67 11.42 vs 56.67 15.25,P < 0.01)significantly;Inflammatory cells infiltration,bronchial stenosis,and airway wall thickening were observed,airway wall thickness area ratio was increased(0.67 0.03 vs 0.58 0.01,P < 0.01),structural remodeling was obviously changed;radial alveolar count(RAC)was increased significantly(15.67 2.70 vs 19.93 5.41,P < 0.05).Conclusion Neonatal hyperoxia exposure can obviously aggravate the airway inflammation of ovalbumin induced asthma model mice,and remodel airway structure,but the lung injury is reduced.Establishment of asthma animal model in children by early postnatal hyperoxia exposure combined with early ova inductionObjective This study aims to investigate whether it is feasible to establish a type of childhood asthma mice model by the combination of neonatal hyperoxia and early OVA sensitization.Methods 64 female BALB/c newborn mice were randomly divided into 8 groups: 2W Air-PBS group,2W Hyperoxia-PBS group,2W Air-OVA group,2W HyperoxiaOVA group,4W Air-PBS group,4W Hyperoxia-PBS group,4W Air-OVA group and 4W Hyperoxia-OVA group,with 8 mice in each group.Hyperoxia group(2W Hyperoxia-PBS group,2W Hyperoxia-OVA group,4W Hyperoxia-PBS group and 4W Hyperoxia-OVA group)was exposed to hyperoxia(Fi O2 ? 95%)for 7 days in 4h after birth,while Air group(2W Air-PBS group,2W Air-OVA group,4W Air-PBS group and 4W Air-OVA group)was raised in room air(Fi O2 = 21%).After 7 days of exposure,the Hyperoxia group was removed from the hyperoxia environment and raised in the same indoor air as the Air group.After 2 weeks of age,mice in 2W Air-OVA group and 2W Hyperoxia-OVA group were given intraperitoneal injection of suspension sensitizing solution [OVA 1mg/ml + Al(OH)3 1mg/ml] 100 ?l.At the same time,2W Air-PBS group and 2W Hyperoxia-PBS group were treat by the same amount of PBS.Meanwhile,mice in 4W Air-OVA group and 4W Hyperoxia-OVA group were given intraperitoneal injection of sensitizing solution [OVA 1mg/ml + Al(OH)3 1mg/ml] 100 ?l after 4 weeks of age and challenged by inhalation of 1% OVA.4W Air-PBS group,4W Hyperoxia-PBS group were treat with the same amount of PBS instead.The mice of 2W and 4W groups were sacrificed at the age of 36 days and 50 days,respectively.BALF was collected for leukocyte counting.The levels of IL-5 and IL-13 in BALF and serum Ig E were detected by ELISA and pathological changes of lung tissue were observed by HE staining.Results: Mice in 2W Air-OVA group and 2W Hyperoxia-OVA group did not show asthmatic symptoms such as wheezing,shortness of breath,scratching ears and gills after OVA challenge.The result of comparing with 2W Air-OVA group ? 2W Hyperoxia-OVA group and 2W Air-PBS group,there was no significant increase of eosinophils counts in BALF along with IL-5,IL-13 levels and serum Ig E levels;Pathological examination of lung tissue showed that the thickness of bronchial wall and the ratio of bronchial wall to total airway area did not increase in each group,there was no obvious changes in morphology of bronchus in each group.After sensitization,mice in 4W Air-OVA group did not show asthmatic symptoms such as crouching,shortness of breath,wheezing and scratching ears and gills,and there was no significant increase in eosinophil counts and serum Ig E in BALF;IL-5 was increased but IL-13 was not in BALF.Pathological examination of lung tissue showed that the columnar epithelium of the airway was hypertrophic,but there was no significant increase in lumen stenosis and airway wall thickness.After sensitization,mice in 4W Hyperoxia-OVA group showed obvious asthmatic symptoms,such as crouching,shortness of breath,wheezing,scratching ears and gills.And the levels of eosinophils counts and IL-5,IL-13 were increased significantly in BALF.The level of serum Ig E was also increased;Pathological examination of lung tissue showed that the airway wall was obviously thickened,and the ratios of airway wall and the total area of the airway are increased.Airway stenosis along with hyperplasia of airway epithelium were also observed in this group.Conclusions: This study confirmed that the mice model of childhood asthma which showing reflation of pathological characteristics of Th2 high asthma in children could be established by neonatal hyperoxia exposure combined with 4-week-old OVA sensitization in female BALB/c mice. |
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