Effects And Mechanisms Of Sevoflurane Inhalation On Airway Inflammation In Asthmatic Mice

Background Asthma is a chronic airway inflammatory disease with complex pathogenesis,which involves a variety of cells and cell components.Asthma is a heterogeneous disorder with variable degrees of inflammation,bronchial hyper-reactivity,mucus hypersecretion and airway remodeling.The commonly used inhalational anesthetic agent sevoflurane(SEV)has been demonstrated to be useful in alleviating allergic airway inflammation,but the underling molecular mechanism is still not clear.Water-specific channel aquaporin5(AQP5)locates in lung alveolar epithelia cells and plays a major role in maintaining osmolality balance in lung.Some studies showed that expression of AQP5 was altered by the inflammation in lung.In the current study,we used an OVA-induced allergic mice model of airway inflammation to investigate the possible involvement of aquaporin-5 in the anti-inflammatory effects of sevoflurane.Methods1.Establishment of acute asthma model: Twenty-four SPF female mice were randomly divided into three groups: Control group(treated with saline),OVA group(ovalbumin sensitization/ ovalbumin challenge),SEV(ovalbumin sensitization/ovalbumin challenge and treated with 3% SEV).Mice in OVA group and SEV group were sensitized with 10?g OVA(sigma,St Louis,MO,USA)emulsified in 1mg alum(Potassium aluminum sulfate,Sango Biotech,Shanghai,China)by intraperitoneal injection on days 0.Mice were than challenged for 30 minutes daily with an aerosol of 1% OVA on days 14-21 after the initial sensitization.3% SEV was administrated before each challenge in SEV group.Mice in control group received normal saline intraperitoneally and aerosolly.2.Evaluation of airway inflammation: Bronchoalveolar lavage was performed at 24 h after the last challenge,and bronchoalveolar lavage fluid was collected.Inflammatory cells in bronchoalveolar lavage fluid were counted and the levels of IL-13 and IL-10 were measured by ELISA method.3.Detection of AQP5 protein expression: The expression of AQP5 protein in lung tissue was detected by immunohistochemistry and Western blot method.Results1.Establishment of a mouse model of acute asthma: As compared with the control group,mice OVA group were irritable,shortness of breath and increased in urine.Histopathological and molecular biological tests showed that the alveolar wall structure was not complete in the lung tissue of asthmatic mice,with large numbers of inflammatory cells infiltration around the bronchi and blood vessels.The total and differential inflammatory cell counts in bronchoalveolar lavage fluid group were increased in OVA group.The levels of TNF-? and IL-13 were augmented(P<0.05)while the level of IL-10 was reduced(P<0.05).2.Inhibition of sevoflurane on airway inflammation in asthmatic mice: As compared with OVA group,the structure damage of lung tissue and the infiltration of inflammatory cells in SEV group was significantly improved.The inflammatory cells count and differential number in bronchoalveolar lavage fluid group were decreased in OVA group.The levels of TNF-? and IL-13 were reduced while the level of IL-10 was augmented(P<0.05).3.Effects of sevoflurane on expression of AQP5 in lung tissue of asthmatic mice: As compared with the control group,the expression of AQP5 protein were reduced greatly in OVA group;compared to OVA group,the expression of AQP5 protein were significantly increased in SEV group mice(P<0.05).Conclusion This study elaborated that sevoflurane inhibited the airway inflammation of asthmatic mice and the inhibition of airway inflammation might be mediated by up-regulation of AQP5 protein expression...