Effects Of Montelukast On Expression Of IL-25,IL-12 And NF-κB,MMP-9 In Asthmatic Model

Objective:1.To investigate the correlations and levels of NF-κB,MMP-9 and the disequilibrium of Th1/Th2 with asthma,we measured the levels of IL-25,IL-12in serum and the expressions of NF-κB,MMP-9 in trachea in asyhmatic mouse.2. To evaluate the relationship between cysteinyl leukotriene receptorl: antagonist MK with IL-25,IL-12,NF-κB,MMP-9 about controltrachea inflammation and trachea through the comparisons of the change of the levelsof IL-25, IL-12 in serum and the expressions of NF-κB,MMP-9 in trachea between the asyhmatic mouse group and the asyhmatic mouse treatgroup(treat with Montelukast).Methods:Weselected 30 wistar mouse.The weight (160±20)g.The mouse were randomized into asyhmatic mouse group(n=10),control group(n=10) and MK treated group(n= 10).Sensitized wistar mouse were challenged by ovabumin(OVA)to establish the Acute asthmatic model.Five mg/kg of MK(MK group)or saline(saline group)were given By stomach for seven days.Samples were collected at 24 th after the last OVA challenge.Cytokines expression levels in the lung,and serum were determined by enzyme-linkedimmunosorbent assay(ELISA).Cellular infiotration in lung tissue was observed with HE and Congo Red stain.Expression of NF-κB and MMP-9 were observed by immunocytochemistry.Compare the result with statistics software SPSS 14.0.Statistical analysis was performed using one-wayANOVA,thelinearregression and correlation.P-value<0.05 were considered as significant.Results:1. The serum IL-25 level in asyhmatic model group was significantly higher than those in MK treated group and control group.(p<0.05),(asythmatic model group:40.71±3.87,MK treated group:34.22±1.37,control group: 25.69±1.74).The IL-25 levels in MK treated group was higher than control group.(p<0.05).2. The serum IL-12 level in asyhmatic model group and those in MK treated group was significantly reducedthannormal mouse(p<0.05).(asythmatic model group:25.91±3.20,MK treated group: 28.75±2.61, control group:33.71±2.69). The IL-12 levels in MK treated group was higher than control group(p<0.05).3. The expressions of NF-κB in trachea in asyhmatic model group was significantly higher than those in MK treated group and control group(p<0.01).(asythmatic model group:0.3422±0.0324,MK treated group: 0.2558±0.0321,control group:0.1580±0.0333). The expressions of NF-κB in trachea in MK treated group was higher than control group(p<0.05).4.The expressions of MMP-9 in trachea in asyhmatic model group was significantly higher than those in MK treated group and control group(p<0.01).(asythmatic model group:0.2779±0.0202,MK treated group: 0.2255±0.0221,control group:0.1674±0.0130). The expressions of MMP-9 in trachea in MK treated group was higher than control group(p<0.05).5.The serum IL-25 level was negatively correlated with the serum IL-12 level in asyhmatic mouse(r=-0.728,p<0.05).Thelinear regression equation was:Y=67.135-1.140X.6.The serum IL-25 level was negatively correlated with the NF-κB level in asyhmatic mouse(r=0.809,p<0.05).Thelinear regression equation was:Y=17.00+65.641X.7. The expressions oflL-12 in serum was positively correlated with the expressions of NF-κB in trachea in asyhmatic mouse(r=-0.659,p<0.05).8. The expressions of NF-κB in trachea was positively correlated with the expressions of MMP-9 in trachea in asyhmatic mouse(r=0.835,p<0.05).Conclusions:1. The serum IL-25 level in asyhmatic mouse group elevated and have the function of promoting inflammation development. 2. Therewas a negatively correlation between the concentration of IL-25 and IL-12.The results indicate that imbalance of Th1/Th2 subsets with inhibition of Thl and predominance of Th2 exist in asthmatic subjects.3. In asyhmatic mouse,the expressions of NF-κB in trachea was positively correlated with the expressions of MMP-9 in trachea.It is concluded that the cooperation of NF-κB and MMP-9 to inflammation and trachea refoud of asthma.4. MK is a effective medication for asthma.