| Background Bronchial asthma is chronic inflammatory airway diseases in that a variety of cells and cytokines were involved.Doctrine of asthma pathogenesis includs the doctrine of airway inflammation,neural-receptor imbalance theory,immune and allergy theory,and so on,in which the immune-inflammatory mechanism is currently one of the mainstream theory of pathogenesis of asthma.T helper cell17(Th17cells) and its cytokine interleukin IL-17were involved in airway inflammation and airway remodeling. Montelukast is a novel non-steroidal drugs for the treatment of asthma.It can effectively reduce airway hyperresponsiveness,improve lung function.Even it has certain effects of antiinflammatory and inhibition of airway remodeling.However,the mechanism of montelukast on airway inflammation and airway remodeling has not been determined.Objectives By studying the effect of montelukast on the expression of helper T cell (Th)17,IL-17and pathological changes of lung tissue in asthmatic rats,and to explore the mechanism of montelukast of inhibition airway inflammation and airway remodeling in asthmatic rats,offer expermental basis for its clinic applying..Methods Thirty clean Sprauge-Dawley(SD) rats were divided randomly into three groups on average:the control group(group C),the asthma model group(group A),the montelukast treatment group (group M). Each group contained ten rats.By OVA sensitized and excited to establish the asthmatic rats in Model group and treatment group.Rats in the A group and M group were sensitized intraperitoneally with100mg of OVA and100mg of Al(OH)3in1mL of normal saline on the first and eighth days.The rats were challenged by2%OVA continuous inhalation from the15th day,30minutes per day for8weeks.The rats in M group were separately given montelukast (10mg.kg-1.d-1) daily by orally before atomizing challenged every time.The rats in C group were sensitized intraperitoneally on the first and eighth days with1mL of normal saline. From the15th day,the rats inhaled normal saline for30minutes per day for8weeks.Twenty-four hours after the final antigen challenge,the rats in every group were executed.Total cells and cell proportions in bronchoalveolar lavage fluid (BALF) were observed.The proportion of Th17cells of blood mononuclear cells were detected by Flow cytometry.Serum IL-17levels were measured by enzyme-linked immunosorbent assay (ELISA).Collected the right lung tissue and then made into pathological sections. Pathological changes of lung tissue were evaluated by HE staining.The parameters of airway remodeling were determined by medical image analysis system.Multiple samples mean were compared using ANOVA, two sample mean using t-test,correlation analysis of two variables mean using Pearson linear correlation analysis.Results (1)The general condition changes in each group:There was no significant symptom in control group.Rats in model group appeared symptoms such as tachypnea, restlessness,unresponsive, scratching fur on their face and gatism,incontinence among or after the challenge. And fur of the rats lost luster, weight growth slow obviously. Compared with the model group,the symptom of rats in montelukast treatment group alleviated obviously.(2)The conditions of inflammation cells in BALF:The total cell numbers,the rates of eosinophils and neutrophils to the total cell numbers in BALF of montelukast treatment group were significantly lower than that in asthma group(P<0.01), but higher than that in control group(P<0.01).(3)The changes in proportion of Th17cells and the level of IL-17in serum: Differentiation of Thl7cells and the level of IL-17in montelukast treatment group was significantly lower than that in Model group(P<0.01), but higher than that in the control group(P<0.01).(4)The pulmonary histopathological changes in each group:A large number of bronchus and vessel lymphocytes, eosinophils, neutrophils and macrophagocytesin filtration,cilia depigmentation, airway wall thickening and other changes were displayed in model group, but the above changes were significantly reduced in montelukast treatment group. The above-mentioned changes were not significant in control group.(5)The determination of parameters of airway remodeling:the thickness of airway wall and smooth muscle in montelukast treatment group were significantly lower than that in asthma group(P<0.01),but higher than that in control group(P<0.01).(6)The results of correlation analysis:There was a significantly positive correlation between the thickness of smooth muscle and proportion of Th17cells and the level of IL-17in serum (r=0.904, P<0.01; r=0.964, P<0.01). There was a significantly positive correlation between PMN numbers and proportion of Th17cells and the level of IL-17in serum (r=0.803, P<0.901; r=0.988, P<0.01).Conclusions Montelukast can reduce airway inflammation and inhibit airway remodeling in asthmatic rats through inhibiting Thl7differentiation and secretion of its inflmmtory meditors. |
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