Effect Of CysLTs On Airway Remodeling In COPD Rats And The Intervention And Mechanism Of Montelukast

Objective: To investigate the effect of Cys LTs on airway remodeling in COPD rats and the effect of montelukast on COPD airway remodeling.Methods: Forty male Wistar rats with SPF were randomly divided into normal control group(group A),COPD group(group B),low-dose montelukast treatment group(group C),and high-dose montelukast treatment group.(D group).Rats in the control group were normally reared,COPD group,low-dose montelukast group,and high-dose Montelukast group rats were treated with intratracheal instillation of lipopolysaccharide(LPS)combined with daily smoking cigarettes to establish rat COPD.model.The rats in the low-dose montelukast group and the high-dose montelukast group were given intragastric administration of montelukast(1 mg/kg)and montelukast(4 mg/kg)in the last 2 weeks,respectively.After 2 weeks of treatment,bronchoalveolar lavage fluid(BALF)was collected to count the total number of white blood cells in BALF and the proportion of various types of inflammatory cells.Pathological sections of lung tissue were taken for HE and Masson staining,and pathological sections were scored for inflammation.Airway inflammation and remodeling of lung tissue were observed.The computer-aided image analysis system was used to determine the total area of ??the airway wall(WAt),airway smooth muscle area(WAm),and basement membrane perimeter(Pbm).The relative thickness of the airway wall was expressed as WAt/Pbm and WAm/Pbm,respectively.And airway smooth muscle relative thickness.The concentration of Cys LTs in rat serum was measured by ELISA,and the expression of b-FGF in lung tissue was detected by immunohistochemistry.Results: At the end of the experiment,none of the rats in each group died.(1)Compared with the normal control group,the number of white blood cells,neutrophils,eosinophils,and airway inflammation scores in BALF of COPD rats increased,airway wall relative thickness(WAt/Pbm)and airway The relative thickness of smooth muscle(WAm/Pbm)was significantly increased(P<0.05).(2)Cys LTs levels in COPD group were significantly higher than those in control group.Correlation analysis showed that serum Cys LTs concentrations in COPD group were positively correlated with airway inflammatory scores and bronchial smooth muscle thickness(r=0.80,P < 0.05;r = 0.89,P <0.05).(3)The total number of leukocytes,the ratio of neutrophils,the ratio of eosinophils,and the score of airway inflammation in BALF in low-dose montelukast and high-dose montelukast groups were lower than those in COPD group.Airway wall Thickness and airway smooth muscle thickness were also lower than COPD group(P < 0.05).(4)The expression level of b-FGF in lung tissue of COPD group was significantly higher than that of control group.Correlation analysis showed that the expression level of b-FGF in lung tissue of COPD group was positively correlated with airway smooth muscle thickness(r = 0.78,P <0.05).The expression of b-FGF in the low-dose montelukast and high-dose montelukast groups was significantly lower than that in the COPD group(P<0.05).The above indicators were not significantly different between the low-dose montelukast group and the high-dose montelukast group(P>0.05).Conclusion:(1)Airway inflammation in COPD is not only related to neutrophils but also to eosinophils.(2)Cys LTs are produced by eosinophils and are associated with airway inflammation and airway remodeling in COPD.(3)Montelukast as a Cys LTs receptor antagonist can inhibit COPD airway inflammation and remodeling.(4)B-FGF is associated with airway remodeling of COPD.Montelukast can reduce the expression of b-FGF in lung tissue of COPD.This may be one of the mechanisms of montelukast in suppressing COPD airway remodeling.