Rolipram Pde Activity Of Rat Model Of Asthma

Objectivewe used the repeatedly ovalbumin(OA) sensitized and challenged Sprague dawley(SD) rats as the asthmatic model to compare pulmonary function and phosphodiesterase (PDE) activity and IL-4 level in the lung tissue of model rats with the normal.rats, and observe the effects of the classical phosphodiesterase 4 inhibitor rolipram on pulmonary function, PDE activity and IL-4 level in the lung tissue.MethodsSD rats were sensitized with OA and heat-killed B. pertussis organisms, and were challenged repeatedly by OA for 7 days. Dynamic lung compliance and pulmonary resistance were determined using a single chamber whole body plethysmogranph. PDE reaction was performed in the assay buffer PBS which contained 10 μlung tissue homogenate of the rats and substrate cGMP and cAMP concentration were 1 μmol L~-1. The cGMP-PDE and cAMP-PDE activity was determined by HPLC measurement of the substrate level of cGMP and cAMP. IL-4 level in the lung tissues was determined by ELISA .The protein concentration was determined by the Bradford colorimetric method with Coomassie blue as the reagent and using bovine serum albumin as a standard. Bronchial alveolar lavage fluid (BALF) and peripheral blood slides were prepared after the rats were killed. The differential white cell count in BALF and in peripheralblood were performed. The data were expressed as x|- ± s .A statistical analysis was performedsingle one-way ANOVA or nonparametric test.Results1. Effect of Rolipram on pulmonary function of repeatedly OA challenged sensitized rats :Dynamic lung compliance of repeatedly OA challenged sensitized rats was significantly lower than the control rats while the pulmonary resistance was significantly higher (P <0.05). Dynamic lung compliance of Rolipram(0.1 mg/kg) treated OA challenged sensitized rats was significantly increased (P <0.05) while pulmonary resistance changes were not statistically significant compare with model. Pulmonary resistance Rolipram(0.1 mg/kg) treated OA challenged sensitized rats was significantly decreased (P <0.05) but not statistically significantincreased dynamic lung compliance changes. Rolipram(0.3 mg/kg) and Rolipram(l mg/kg ) increased dynamic lung compliance and decreased pulmonary resistance of OA challenged sensitized rats significantly (P <0.05). Dexamethasone(0.1 mg/kg, 0.5mg/kg) also significantly decreased the pulmonary resistance and increased dynamic lung compliance.2. Effect of rolipram on cGMP-PDE, cAMP-PDE and PDE4 activity in lungs of repeatedly OA challenged sensitized rats:The cGMP-PDE. cAMP-PDE and PDE4 activity in lungs of repeatedly OA challenged sensitized rats were singnificantly increased than the control rats (P <0.05 ). rolipram significantly decreased the increased cAMP-PDE and PDE4 activity in lungs of repeatedly OA challenged sensitized rats. The cGMP-PDE activity in lungs of rolipram (0.1 mg/kg) and rolipram (0.3 mg/kg ) rats did not change significantly compared with repeatedly OA challenged sensitized rats while rolipram (1 mg/kg ) decreased the increased cAMP-PDE activity in lungs of OA challenged sensitized rats with significance (P <0.05 ). Dexamethasone( 0.1 mg/kg, 0.5mg/kg ) also significantly decreased the increased cAMP-PDE and cGMP-PDE activity( P <0.05 ).3. Effect of rolipram on IL-4 level in lungs of repeatedly OA challenged sensitized rats :IL-4 level in the supernatant of repeatedly OA challenged sensitized rats in lung homogenates was singnificantly increased compared with control rats (P <0.05 ). Rolipram ( 0.3 mg/kg ) and rolipram (1 mg/kg ) decreased the increased IL-4 level of lung in repeatedly OA challenged sensitized rats singnificantly (P <0.05). Dexamethasone ( 0.1 mg/kg, 0.5mg/kg ) significantly decreased the the increased IL-4 level of asthmatic rats (P <0.05 ).4. Rolipram markedly significantly reduced total cell counts and eosinophil counts in BALF of OA challenged sensitized rats (P<0.05).5. Rolipram markedly significantly reduced eosinophil counts in peripheral blood of OA challenged sensitized rats (P<0.05).6. Spearman correlation analysis showed t...