The Effects Of Leukotriene Receptor Antagonist Combined With Glucocorticoid On Airway Inflammation Of Asthmatic Rats

Objective: In order to search for an effective combined treatment plan for parts of asthmatic children needing large-dose glucocorticoid treatment, the experiment basing on the asthmatic animal models observed the effects of Leukotriene receptor antagonist combined with glucocorticoid on airway inflammation of asthmatic rats, and tried to confirm the combination can decrease the dose of glucocorticoid and exert better anti-inflammation effects, and provide animal experimental foundation for instructing clinical therapy.Methods: 40 Wistar rats(one half was male)were randomly divided into five groups :normal control group, the asthmatic model group, montelukast group(MK group), dexamethason group, MK and dexamethason combination treat group .There were 8 rats in each group.On the first and seventh day, every group except for the normal control group was injected to intraperiton with 1ml antigen liquid (100mg egg albumin and aluminum hydroxide powder 100mg) to cause the rats being allergized. The normal control group was treated with equal normal sodium instead of antigen liquid. On the fourteenth day, rats were placed in a plexiglass box incompletely closed and were stimulated by 1% egg albumin with compression atomizer, one time a day, lasted for 20 minutes ,for 10 days. The normal control group was treated with equal normal sodium instead of OVA. On the seventeenth day , drugs were administered to the rats of every group except for the normal control group and model group at 30 minites before being stimulated. MK group was gavaged with MK (2mg per rat),dexamethasone group was gavaged with dexamethasone (0.15mg per rat),combination group was gavaged with MK(1mg per rat) and dexamethasone (0.075mg per rat).one time a day ,lasted for 7 days. The normal control group and the asthmatic model group were gavaged with equal normal sodium.On the twenty-third day, within 12 hours after the last stimulus, the blood of all rats was obtained by head-breaking for testing indexes. After that ,every rat was fixed on operation table , then isolated trachea, ligated the right lung and the left lung was infused with 2ml normal sodium at 37 centidegree by tracheal intubation, and laundered back and forth twice ,then collected bronchoalveolar lavage fluid. Peripheral eosinophils count was detected by conventional counting method. The concentrations of IFN-γand IL-4 in serum and BALF were measured by ELISA. The concentration of NO in serum was tested by nitricacid reduction method and ET-1 in serum was tested by radioimmunoassay.Results:1.Comparison of the count of EOS in peripheral blood of every group The count of EOS in peripheral blood of model group was higher compared with that of normal group,there was a very significant difference (P<0.001); The counts of EOS in peripheral blood of all drug treatment groups were lower compared with that of model group, the counts of EOS of dexamethasone group and drug combination group were significantly different from that of model group(P<0.01), but The counts of EOS of MK group and model group were no significant differences (P>0.05);The count of EOS of MK group was higher than that of dexamethasone group (P>0.05);The count of drug combination group was lower than that of dexamethasone group, but there was no significant difference between two groups(P>0.05); The count of EOS of MK group was higher compared with that of drug combination group (P>0.05).2.Comparison of the concentrations of IFN-γin serum and BALF of erery groupThe concentrations of IFN-γin serum and BALF of model group were lower than those of normal group,there were very significant differences (P<0.001);The concentrations of IFN-γin serum and BALF of all drug treatment groups were higher than those of model group (P<0.01);The concentrations of IFN-γin serum and BALF of MK group were lower compared with those of dexamethasone group (P<0.01); The concentration of IFN-γof drug combination group was lower than dexamethasone group,but there were no significant differences between drug combination group and dexamethasone group (P>0.05); The concentration of IFN-γof MK group was lower than those of drug combination group, there were significant differences between two groups(P<0.05).3.Comparison of the concentrations of IL-4 in serum and BALF of erery groupThe concentrations of IL-4 in serum and BALF of model group were higher compared with those of normal group,there were very significant differences(P<0.001);The concentrations of IL-4 in serum and BALF of all drug treatment groups were lower than those of model group, the concentrations of dexamethasone group and combination group were significantly different from those of model group(P<0.01), there were also significant difference between MK group and model group(P<0.05);The concentrations of IL-4 in serum and BALF of MK group were higher than those of dexamethasone group (P<0.01);The concentration of IL-4 in serum and BALF of drug combination group were lower than those of dexamethasone group (P>0.05); The concentrations of IL-4 in serum and BALF of MK group were higher than those of drug combination group(P<0.01).4.Comparison of the ratio of IFN-γ/IL-4 in serum and BALF of every groupThe ratio of IFN-γ/IL-4 in serum and BALF of model group was lower compared with that of normal group (P<0.001);The ratio of IFN-γ/IL-4 in serum and BALF of all drug treatment groups was higher than that of model group (P<0.01); The ratio of IFN-γ/IL-4 in serum and BALF of MK group were lower than that of dexamethasone group (P<0.01); The ratio of IFN-γ/IL-4 in serum of drug combination group was higher than that of dexamethasone and the ratio of IFN-γ/IL-4 in BALF of drug combination group was lower than that of dexamethasone, but there were both no significant difference between two groups(P>0.05). The ratio of IFN-γ/IL-4 in serum and BALF of MK group were lower than that of drug combination group (P<0.01).5.Comparison of the concentration of NO in serum of every groupThe concentration of NO in serum of model group was higher than that of normal group (P<0.001);The concentrations of NO in serum of all drug treatment groups were lower compared with that of model group, the concentrations of NO in serum of MK group and combination group were significantly different from that of model group(P<0.05), and there were also significant differences between dexamethasone group and model group(P<0.01); The concentration of NO of MK group was higher than that of dexamethasone group, there were no significant difference between two groups(P>0.05); the concentration of NO of combination group was higher than that of dexamethasone group (P>0.05). The concentration of NO of MK group was higher compared with that of drug combination group (P>0.05). 6.Comparison of the concentrations of ET-1 in serum of erery groupThe concentration of ET-1 in serum of model group was higher than that of normal group (P<0.001); The concentrations of ET-1 in serum of all drug treatment groups were lower compared with that of model group, the concentrations of ET-1 of dexamethasone group and combination group were significantly different from that of model group(P<0.01), The concentration of ET-1 of MK group was also significantly different from that of model group(P<0.05); The concentrations of ET-1 of MK group was higher than that of dexamethasone group(P>0.05);The concentration of ET-1of drug combination group was lower than dexamethasone group(P>0.05); The concentration of ET-1 of MK group was higher compared with that of drug combination group,there was a significant difference between two groups (P<0.05).Conclusions: Leukotriene receptor antagonist montelukast can exert accommodative effects on Th1/Th2 imbalance and contents of NO and ET-1. It combinated with small-dose glucocorticoid can effectively improve the airway inflammation of asthmatic and achieve the equal effects with large-dose glucocorticoid on eliminating inflammatory cells, facilitating immunity recover, mediating nerval factors and so on.