Experimental Study Of Steroid Resistant Asthma Animal Models In Mice

Objective:The study intended to explore the effective steroid resistant asthma animal models in mice.Methods:Common 30 female BALB/C mice were randomly divided into 5 groups: normal control(NC), untreated asthma(NTA), steroid sensitive asthma(SSA), airway remodeling(AR) and steroid resistant asthma(SRA) groups, each group of 6. The NC group not any processing, directly put to death. Mice of NTA, SSA, AR and SRA were sensitized intraperitoneal on day 0, 7 and 14 with 50μg ovalbumin(OVA) in Alum and challenged with aerosol inhalation of 1% OVA starting from day 21, 30 min a day for five consecutive days. 30 minutes prior to the second atomization for 2 days in SSA mice celiac injection of dexamethasone(DEX)(2 mg/kg). AR and SRA groups challenged nine consecutive weeks. At the same time, SRA mice intraperitoneal injection of DEX according to SSA group, twice a week for nine consecutive weeks. For control, NTA and AR group was used 0.9% physiological saline to instead of DEX injection.Twenty-four hours after the final inhalation and challenge, all the mice were sacrificed for determining the concentration of inflammatory cells in the bronchoalveolar lavage fluid(BALF).Lung tissue samples were taken for counting and classifying infiltrating cells, for anglicizing the thickness of airway wall and smooth muscle.Results:All mice of four treated groups had asthma symptoms for example harassment in the first atomization systemic. Accompanied with an increasing number of atomization,AR and SRA mice symptoms were aggravated gradually and treatment reactivity of DEX in SRA mice was decreased. Persistent wheezing since atomization sixth week mice appeared, at this point DEX can’t cure whoop. In NTA group the epithelial cell in bronchial felt off, mucous membrane disrupted, goblet cells were at the top of the cavity, bronchial submucosal and pervascular was observed obvious cell infiltration. The SSA group had intact bronchial mucosa and was significantly lighter than NTA in goblet cells hypersecretion and inflammatory cells infiltration. Both in AR and SRA groups, bronchus fold increased, epithelial cells proliferated obviously disorder induces to luminal stenosis and lober atelectasis,the smooth muscle cells in bronchus and vascular proliferated too, more heavier inflammatory cells infiltration was observed. SRA group was more serious about alveolar rupture and fusion, to pulmonary bullae formation. Total cell count in BALF of NTA, AR and SRA groups were significantly higher than that of normal control group(NC)(P < 0.01). The number of eosinophil,neutrophil and lymphocyte counts in lung and the thickness of airway wall, smooth muscle of four asthmatic mouse modeling were significantly higher than the NC group(P < 0.05). SRA mice were more series than SSA in inflammatory cells seepage in BALF, in eosinophil and lymphocyte infiltration in lung tissue and in airway wall, airway smooth muscle thickness(P < 0.01). And AR group was more series than NTA both in inflammatory cells seepage in BALF and in airway wall, airway smooth muscle thickness(P < 0.05). Compare SRA with AR, only eosinophil counts increased obviously(P < 0.01).Conclusions:1.The hormone could reduce cells infiltration both on eosinophil and lymphatic, but not neutrophil. 2. Repeated antigen stimulation combined with interruption of hormone therapy might cause eosinophil and lymphatic infiltration increases, and also might cause airway remodeling and lung damage, and then lead to the deterioration of the asthma symptoms, even more hormone resistance.3.The DEX treatment on SRA group had been observed and been a failure or even worse before sacrifice. Lung tissue pathology was found significant inflammatory cells infiltration(mainly of eosinophil, neutrophil) and airway remodeling, so this method for building steroid resistant asthma animal model may be really feasible.