The Effect Of Ambroxol Hydrochloride Combined With Budesonide Suspension On Airway Inflammation And Oxidative Stress In Rats With Asthma

Objective To investigate the effect of Ambroxol hydrochloride combined with Budesonide suspension on airway inflammation and levels of oxidative stress in the lung of rats with asthma.Methods Thirty-two male Wistar rats were divided randomly into a control group, a sensitized group, a Budesonide Suspension-treated group(BUD) and a group treated by ambroxol hydrochloride combined with Budesonide Suspension(AMB+BUD). The cell in Bronchoalveolar lavagfluid(BALF) of each group was classified and count. The lung tissue was pathologically observed through hematoxylin and eosin staining, and the level of ROS and GSH in the lung were measured respectively. The expressions of y-GCS and Nrf2 in lung were measured by immunohistochemistry; The expressions of y-GCS-hmRNA and Nrf2mRNA in lung were measured by in situ hybridization.Results 1.Lung inflammation related factors:①Totalcells,eosinophils (EOS%) and lymphocytes ratio (L%)in BALFof AMB+BUD group were significantly lower than the BUD group; those in BALF of sensitized group were higher than other groups(all P<0.05).②HE staining of lung tissue:the bronchial wall inflammation and damage in the BUD+AMB group and the BUD group were significantly reduced compared with sensitized group, which is more significant in the BUD+AMB group.2. oxidative stress-related factors:①ROS in the AMB+ BUD group were significantly lower than that in the BUD group and GSH was significantly higher than that in the BUD group (all P<0.01). ROS in the sensitized group was significantly higher than the other three groups and GSH was significantly lower than the other three groups (all P<0.01);②The expressions of y-GCS-hmRNA and y-GCS protein:both of which in the AMB+BUD group were higher than that in the BUD group (P<0.01); both of which in the sensitized group expression were higher than other groups (all P<0.01); the differences of both of which between the BUD group and the control group was not significant (all P>0.05).③The expression of Nrf2 mRNA and Nrf2:the differences of the expression of Nrf2 mRNA in each group were not significant (all P>0.05). the expressions of Nrf2 in the sensitized group were higher than other groups (P<0.01);that in the AMB+BUD group were higher than that in the BUD group (P<0.01); no significant differences in the expression of Nrf2 exsisted between the BUD group and the control group (P>0.05).3. linear correlation analysis showed that:the total cells, eosinophils and lymphocytes ratio in the BALF were highly positively correlated with the concentration of ROS and were highly negatively correlated with the concentrations of GSH; the expression levels of Nrf2γ-GCS-hmRNA and y-GCS protein were positively correlated with the ROS,and were negatively correlated with the GSH concentrations (P<0.01).Conclusion 1. The lung tissues of sensitized rats had the imbalance oxidation/antioxidant, which had an important role in the pathogenesis of asthma.2. Ambroxol combined inhaled corticosteroids which could significantly reduce the airway inflammation and oxidative stress of lung tissues had synergistic effects on the treatment of asthma attack.3. Ambroxol combined inhaled corticosteroids could increase the expression of Nrf2 and y-GCS,which might be one of their anti-inflammatory and anti-oxidant mechanisms.