The Effect Of Ambroxol On The Expression Of AP-1andγ-glutamylcysteine Synthetase In The Lung Of Asthmatic Rats

Background The classical theory about asthma is the airway inflammation of eosinophils-based infiltration,but in recent years many studies have found that the oxidant/antioxidant imbalance also plays an important role in asthma; Ambroxol is a commonly used expectorants,some studies have found in recent years that it has certain antioxidant effect in the treatment of asthma.Objectives The purpose of this experiment is to investigate the effect of ambroxol on oxidant/antioxidant system of asthmatic rats and its possible mechanisms by observing the pathological changes and lung tissue of asthmatic rats and activator protein-1and y-glutamylcysteine synthetase in bronchoalveolar lavage fluid.Methods Asthmatic rat models were established with the ovalbumin (OVA) sensitization and provocation method.Thirty male Sprauge-Dawley(SD) rats were divided randomly into three groups on average:the normal control group,the asthma group,the ambroxol treatment group.Rats in the asthma group and the ambroxol treatment group were sensitized intraperitoneally on the first and eigth days with100mg of OVA and100mg of A1(OH)3in lml of normal saline.The rats were challenged by1%OVA (w/v) continuous inhalation from the15th day,20minutes every day for7days.Rats in the normal control group were injected with lml of normal saline on the first and eigth days intraperitoneally.From the15th day,the rats inhaled normal saline for20minutes per day for7days.The ambroxol treatment group was treated with ambroxol (50mg.kg-1.d-1) daily intraperitoneally during the period of allergen sensitization and provocation.The normal control group and the asthma group were treated with normal saline.Twenty-four hours after the final antigen challenge,bronchoalveolar lavage fluid(BALF) was collected from all rats.The pathological changes of lung tissue were observed by HE staining,and the expression level of AP-1(c-Jun and c-Fos subunit) and y-GCS in bronchoalveolar lavage fluid were detected by immunocytochemical staining and expression of AP-1(c-Jun and c-Fos subunit) and γ-GCS in lung tissue were observed by immunohistochemistry.Results (1)In the challenge process,the asthma group appeared visible respiratory distress signs(polypnea, cyanose,et al).The asthma group appeared invisible respiratory distress signs compared with the ambroxol treatment group.There is no respiratory distress and so on above in the normal control group.(2)Normal control group:alveolar of uniform size and thin wall, bronchial epithelial integrity and surrounded by almost no infiltration of inflammatory cells and their secretions in the lung tissue of rats. Asthma group:mucosal epithelial edema associated with partial shedding,thickening of basement membrane,increase of mucus glands,infiltration of eosinophils,macrophages and mononuclear cells in the wall layer.Ambroxol treatment group:the extent and severity of disease reduced compared with model group significantly.(3)The expression of AP-1(c-Jun,c-Fos subunit)protein in the lung tissue and bronchoalveolar lavage fluid: the expression of c-Jun and c-Fos protein in the lung tissue and bronchoalveolar lavage fluid increased in asthma group compared to normal control group significantly(P<0.01); The expression of c-Jun and c-Fos protein in the ambroxol treatment group reduced significantly compared to asthma group(P<0.01), but higher than that of the control group(P<0.01).(4)The expression of y-GCS protein in the lung tissue and bronchoalveolar lavage fluid:the expression of γ-GCS protein in the lung tissue and bronchoalveolar lavage fluid in asthma group increased significantly compared to control group(P<0.01); The expression of y-GCS protein in ambroxol treatment group reduced significantly compared to asthma group(.P<0.01), but higher than that of the control group(.P<0.01).Conclusions (1) Ambroxol play the role of antioxidant, this may be related to the decreasing of the level of the AP-1(c-Jun, c-Fos subunit) and γ-GCS protein.(2) Ambroxol alleviate the damage of bronchopulmonary tissue and protect the lung function of asthmatic rats through its anti-oxidant function.