ABSTRACT
Aim Toestablishanexcellentratasthmamodel from using OVA+pertussis sensitized, OVA sensitized and per-tussissensitizedrats.Methods Thethreemethodswereusedto sensitize rats;methacholine bronchial provocation tests were per-formed to determine airway hyperresponsiveness;bronchoalveolar lavage fluid ( BALF) was prepared after the animals were chal-lenged by nebulized antigen. The differential white cell count in BALF was performed, and lung tissue was detected by morpho-logicalanalysis.Results AllofOVA+pertussissensitization,OVA sensitization and pertussis sensitization could deteriorate lung function, increase inflammatory cells and cause pathological change, and OVA + pertussis sensitized rat model had better effect than OVA sensitized and pertussis sensitized rat models. Conclusion OVA+pertussissensitizationandOVAaerosolisa successful rat asthma model.
ABSTRACT
Phosphothesterases [PDE] hydrolyse intracellular cAMP and cGMP to inactive 5' monophosphates Decreased level of cAMP is involved in the pathogenesis of asthma. We and others have shown that phosphodiesterases were upregulated in the lung of allergic rats, and Bacilli Calmette-Guerin [BCG] induced the production of cAMP in vitro. However, it is unclear how BCG's effect asthma and whether it is related to PDEs. In this study, BCG was intraperitoneally injected into male Sprague-Dawley rats sensitrized and later the rats were challenged with ovabumin/pertusis. The inflammation in lungs was measured. Airway hyperresponsiveness was determined using MedLab software after intravenous methacholine challenge. Furthermore cAMP level and adenylate cyclase activity in lungs were analyzed by ELISA, Phosphodiesterases activities were analyzed by HPLC, while PDEs mRNA levels in lungs was analyzed by reverse transcription-polymerase chain reaction. Administration of BCG significantly attenuated allergen-induced lung inflammatory response and hyper responsiveness as compared with vehicle treatment. Furthermore, the levels of cAMP in lungs were significantly increased in BCG-treated allergic rats. Interestingly, administration of BCG decreased the activity of cAMP-PDE, but not adenylyl cyclase [AC], activity in lungs of animals. Furthermore, pretreatment with BCG significantly decreased the mRNA levels of PDE4A, 4C, 5 and 8, which were induced in lungs of allergic rats. BCG administration attenuated airway inflammatory response and bronchial hyper responsiveness in rats, which are the most important symptoms in asthma. The decreased PDEs mRNA and inhibited cAMP-PDE activities by BCG contribute, at least in part, prevention of allergen-induced airway inflammation and asthma in rats
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Aim To investigate the changes of phosphodiesterase4(PDE4,type 4 cAMP-specific PDE) activity,TNF-? and neutrophil recruitment in experimental rat lung injury(ALI).Methods ALI in the rat was induced by lipopolysacdharide(LPS).PDE4 activity was measured with HPLC,and the level of TNF-? was detected with ELISA,neutrophil infiltration in bronchoalveolar lavage fluid(BALF) and lung tissues was detected by cell count and morphological analysis.Result Lung tissue PDE4 activity significantly increased as early as 1 h,peaked 6 h,and then markedly lowered at 24 h after intratracheal administration of LPS,while there was a same time-course change of total white cell and neutrophil in the BALF(r=0.83,P
ABSTRACT
Aim Establish a novel mouse model of airway goblet cell hyperplasia and mucus hypersecretion.Method BALB/c mice were sensitized subcutaneously with ovalbumin(OVA) allergens in aluminium hydroxide at d 0,re-sensitized once intraperitoneally d 10 after first sensitization,and challenged with OVA aerosolly daliy from d 15 to d 21 after first sensitization.Inflammatory cell number in BALF,eosinophil infiltration in the lung tissue with HE stain and goblet cells in the bronchial mucous membrane with PAS stain were examined.Dexamethasone was employed to validate the model.Results Mice sensitized and challenged with OVA showed a significantly hyperplasia of goblet cells in the bronchial mucous membrane,increased mucus in the alveolar cavity,eosinophil infiltration in the lung tissue and increased number of inflammatory cells in BALF.Those pathological changes were inhibited by dexamethasone and mIL-2 plasmid.Conclusion This model helps to screen the new drugs for mucus hypersecretion and research on the pathological mechanism of airway mucus hypersecretion.
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Aim In order to provide the experimental basis to investigate the pathologic mechanisms and drug treatment of pulmonary fibrosis,establish the lung slice fibrosis model induced by transforming growth factor-?_1 (TGF-?_1) . Methods Lung was isolated and inflated with 0.4 % agarose solution, then was cut into slices. The lung slice viability was assessed through lactate dehydrogenase (LDH) leakage and MTT assay after incubation of 1, 3, 5, 7, 9 days. The sub-optimal time and dose of TGF-?_1- induced lung slice fibrosis were investigated via measurement of hydroxyproline (HYP), and lung slice fibrosis was examined with HE and Masson staining. Results The lung slice was viable for up to 9 days. The sub-optimal time and dose of TGF-?_1-induced lung slice fibrosis were 7 days and 2.5 ?g?L~ -1 respectively. Meanwhile, hydrocortisone did not decrease the HYP levels in lung slices of TGF-?_1-induced fibrosis. Conclusion TGF-?_1 (2.5 ?g?L~ -1 ,?7d) induced lung slice fibrosis, and hydrocortisone did not exert advantageous effect on this process.