Effect Of Leukotriene Receptor Antagonist On Wnt/?-catenin Signaling Pathway In Asthmatic Mice

BACKGROUNDBronchial asthma,is a chronic airway inflammation involved and mediated by a variety of inflammatory cells(such as eosinophils,mast cells,smooth muscle cells,T lymphocytes,etc.)and cellular components.The wide range of reversible airway limitation is a main feature of asthma.The repeat occurrence and renovation of inflammation are changing the structure of the respiratory tract,such as:hyperplasia and hypertrophy of smooth muscle,thickening,deformation,fracture of airway basement membrane and fibrin deposition,increased secretion of goblet cells,metaplasia of epithelial cells,which are called airway remodeling.With the development of industry,the incidence of asthma disease is increasing year by year.Therefore,further search for new therapeutic target areas is still a key topic in the field of asthma research.Wnt/beta-catenin signaling pathway plays an important role in the pathological physiology of respiratory system diseases.First,beta-catenin proteins have an important status in maintaining the bronchial airway epithelium structural integrity and the process of signal transduction.Some research shows that beta catenin expression more in asthmatic airway epithelium and airway smooth muscle cells,and is related to airway remodeling.Leukotriene receptor antagonist can play anti-inflammatory,anti fibrosis and ameliorate the early airway remodeling by various signal pathways.The purpose of this study was to explore the relationship between Wnt/-catenin signaling pathway and airway remodeling in asthmatic by studying the mechanism of intervention of leukotriene receptor antagonist on airway remodeling in asthmatic mice,for bring new targets to the treatment of asthma.OBJECTIVETo study the effect of leukotriene receptor antagonist on the expression of ?-catenin,VEGF and MLCK,and on the airway remodeling of asthmatic mice.METHODSThe thirty female BALB/C mice were divided into control group,asthma group,and montelukast sodium group by digital table method,10 mice in each group.Model was sensitized and established by OVA induction,the control group was sensitized by normal saline.He staining was used to observe the pathological changes of lung tissue in mice under the microscope.Enzyme linked immunosorbent assay(ELISA)determined the levels of serum OVA-sIgE,The mRNA levels of?-catenin,MLCK and VEGF in the lung tissue were determined by RT-PCR in lung tissues.Image-pro plus Image analysis software was used to determine the bronchial wall area(WAt)and bronchial smooth muscle area(WAm)in pathological sections,and the bronchial lumen circumference(PBM)was standardized.The data were analyzed by one-way ANOVA,and the LSD-t method was used to compare the differences between two groups,P<0.05 is statistically significantRESULTSHE staining showed that the bronchial wall of mice was thickened and a large number of inflammatory cells infiltrated around the bronchi in the asthma group,while the bronchial wall thickness and the degree of inflammatory cell infiltration in the lung tissue of mice were significantly reduced in the montelustra sodium group The level of OVA-sIgE in the asthma group was significantly higher than that in the control group(P<0.05),the level of OVA-sIgE in the montelukast sodium group was lower than that in the asthma group(P<0.05),and the mRNA levels of-catenin,MLCK and VEGF in the lung tissues of the asthma mice detected by rt-pcr were significantly higher than those in the control groupCONCLUSIONWnt/?-catenin signaling pathway may be an important factor in the pathogenesis of asthma.Leukotriene receptor antagonist(montelukast sodium)may influence the expression of ?-catenin,vegf and mlck in airway remodeling of asthma.