The Effects Of Leukotriene Receptor Antagonist In Preventing And Treating Airway Remodeling Of The Asthmatic Model

Structural changes in the airway walls are essential features of asthma which include extracellular matrix changing, epithelial desquamation, goblet cell hyperplasia, prominent smooth muscle, vascular remodeling, collagen deposition below the basement membrane. These changes are called airway remodeling. Because of airway remodeling, the therapy for asthma is very difficult.Objective To investigate the effect of leukotriene receptor antagonist inpreventing and treating airway remodeling of the asthmatic guinea pig model and provide reliable laboratory evidence of new method for preventing and treating asthma.Methods One hundred and eight pathogen-free male guinea pig(weight320-400g) were randomly divided into three groups : asthmatic was group A (n=36), Zafirlukast therapeutic was group B (n=36), normal saline control was group C (n=36).Each group was divided into six subgroups: 24 hours,1 week,2 week, 4 week, 8 week, 12 week. The symptom and physical sign was observed carefully. The thickness of airway smooth muscle and the infiltration ofinflammatory cells and the epithelial hyperplasia were observed with HE stain. The changes of collagen and vascular proliferation were observed with VG stain. The expression level of vascular endothelial growth factor (VEGF) and tissue inhibitor metalloprotease-l(TIMP-l) in lung tissue and the apoptosis of inflammatory cells were analyzed with immunohistochemistry marked.Results (l)The symptom and physical sign was more obvious in group A than that of group B, there is no symptom and physical sign in group C.(2)Thebronchiolar smooth muscle thickness in group A is higher than that of group B and group C. Eight weeks after stimulating, the differences among three groups were statistically significant(p<0.05).(3) Two weeks after stimulating, the accumulation of inflammatory cells around small airway were obviously higher in group A than that of group B, the apoptosis of inflammatory cells were clearly higher in group B than that of group A, the accumulation of inflammatory cells and the apoptosis cell in group C was little.(4)The epithelial proliferation and abscission in group A was higher than that of group B and C.(5)Four weeks after stimulating, the expression level of VEGF in group A was more than that of group B and C, the differences among three groups were statistically significant(p<0.05). Eight weeks after stimulating, the number of vessels in basement membrane in group A was more than that of group Band C. (6)Eight weeks after stimulating, the expression level of TIMP-1 in group B was more than that of group A and C, Twelve weeks after stimulating the differences among three groups were statistically significant(p<0.05), but eight weeks after stimulating, the collagen deposition in group A was more than that of group B and C.Conclusion Leukotriene receptor antagonist postponed the airwayremodeling in asthma by reducing the inflammatory cells infiltration, smooth muscle hypertrophy, epithelial desquamation, vessels proliferation, collagen deposition and increasing the apoptosis of inflammatory cells, but the role is not complete.