Objective: To reproduce a severe asthma model in ovalbumin (OVA)-sensitized Balb/C mice by induction with respiratory syncytial virus (RSV).
Methods: Thirty Balb/C mice were randomly divided into phosphate buffer solution (PBS) control group, OVA group and OVA/RSV group. The severe asthma model was reproduced by sensitization with intraperitoneal injection of OVA, followed by repeated inhalation of OVA combined with repeated intranasal instillation of RSV (1.0x10(9) pfu/L in 50 microl). Asthmatic symptoms were observed. The changes in airway responsiveness represented by lung resistance (R(L)) stimulated by acetylcholine (Ach) and function of lung in terms of peak expiratory flow (PEF) and the ratio of forced expiratory volume in 0.4 second (FEV 0.4) /forced vital capacity (FVC) were determined. Lung tissue sections with hematoxylin and eosin (HE) staining for general pathology, periodic acid Schiff (PAS) staining for identification of goblet cells mucus secretion and Masson staining for pathologic changes in lung tissue and remodeling were examined. The ratio of inner diameter to outer diameter of the airway, and the thickness of smooth muscle and basement membrane were determined.
Results: (1) The differences in R(L), PEF and ratio of FEV 0.4 /FVC both in OVA/RSV group and OVA group were significant when compared with those in PBS control group when stimulated by Ach (5.0, 15.0 and 45.0 g/L) (respectively P<0.01). Asthma symptoms were more severe in OVA/RSV group, compared with those of OVA group. Total R(L) was increased and PEF and ratio of FEV 0.4 /FVC were decreased in OVA/RSV group compared with those of OVA group (respectively P<0.01). There were more severe bronchoconstriction and more extensive inflammatory cells (eosinophils, lymphocytes, neutrophils) infiltration around the bronchi in the OVA/RSV group. A marked and extensive airway goblet cell hyperplasia and mucus excretion in airway lumen and deposition of collagen in subepithelial basement membrane were found in the OVA/RSV group. (2) The ratio of inner diameter to outer diameter and that of the thickness of smooth muscle and basement membrane were 0.56+/-0.03, (45.12+/-2.08) microm and (36.15+/-1.88) microm, respectively, in OVA/RSV group, and the differences were significant (respectively P<0.01), as compared with OVA group [0.75+/-0.06, (24.63+/-0.94) microm and (21.68+/-1.13) microm, respectively].
Conclusion: An animal model of severe asthma is successfully reproduced by nasal inoculation with RSV in OVA-sensitized Balb/C mice.
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