Effects Of Leukotriene Receptor Antagonist On Airway Remodeling In Asthmatic Mouse Models

Objective Airway inflammation and remodeling in chronic asthma are characterized by airway eosinophilia, lymphocytosis, mastocytosis infiltrate, hyperplasia of goblet cells and smooth muscle, subepithelial fibrosis and submucosal vascular proliferation. We examined the effects of cysteinylleukotriene(CysLT1) receptor antagonist montelukast (MK) and dexamethasone(DXM) on the mediators of airway remodeling, such as VEGF, MMP-2,arginase Ⅰ and arginase Ⅱ, in a mouse model of allergen-induced chronic lung airway inflammation and remodeling, provide further insight into molecular mechanism of MK in asthma intervention.Methods BALB/c mice, after intraperitoneal ovalbumin OVA 100μgsensitization on days 1 and 15, received intranasal OVA periodically days 15-76. At this period, DXM and MK were administered introperitoneally and gastrointestinally. The lung sections were stained with hematoxylin and eosin to assess the inflammatory cell infiltrate, alcian blue staining to identify airway goblet cells. Total RNA was isolated from the right lung of each mouse, and mRNA levels for MMP-2 and arginase Ⅰ , arginase Ⅱ determined using MBI retro transcription kit, MBI PCR kit. VEGF were determined by EIAResults Obvious infiltration of inflammatory cells and proliferation of goblet cells as well as enhancement of mucus and smooth muscle hyperplasia could beseen in the lung of asthmatic mice. After the treatment of MK and DXM, the decrease of the above mentioned effects and MMP-2, arginase I , arginase II in the tisssue and VEGF in the serum were observed. The amount of MMP-2, arginase I , arginase II of asthmatic and MK treated mice were measured as 1.61±0.15, 1.40±0.13, 2.06±0.24 and 0.27±0.04 0.23±0.04 0.55±0.09, respectively. The concentration of VEGF in serum of asthmatic mice (5.71±1.61ng/ml) was significantly higher than that of MK treated mice(2.02±0.95ng/ml, P<0.05). Compared to MK, the effects of DXM on the arginase I , arginase II, MMP-2 and VEGF (0.21±0.03, 0.40±0.07, 0.29±0.04, 3.11 ± 1.23) were not proved to be of statistically significance(P>0.05).Conclusions The MK and DXM significantly reduced the airwayinflammatory cells infiltration, mucus plugging, smooth muscle hyperplasia and remodeling related factors in the OVA-sensitized/challenged mice. These data suggest an important role for MK and DXM in the pathogenesis of chronic allergic airway inflammation with fibrosis.