The Research Of Dynamic Changes And Mechanism Of Th17 Cell/ CD4~+CD25~+Treg Cell In Airway Remodeling After Leukotriene Receptor Antagonist Intervene Asthmatic Mice

Objective:Discussion of Thl7 cells,CD4+CD25+regulatory T cell s,TGF-betal,smad2,smad7 protein variation and relation with airway remo deling after Leukotriene receptor antagonist montelukast intervene asthmati c mice.Provide laboratory evidence for clinical prevention and treatment o f asthma.Method:Divided Balb/c rat into three groups randomly(24 per gr oup), blank group(group A)?asthma group(group B)?montelukast group(g roup C).group B and group C will be sensitized by intraperitoneal injecti on of chicken ovalbumin (OVA) and aluminum hydroxide suspension at 0,14 per day.And blank group were be given the same amount of NS by peritoneal injection. From 21 day,group B, group C will be given OVA suspension by atomization inspiration for about 30 minutes,every other da y.Group A were aerosol inhaled of the same amount of NS.Group C wer e given montelukast suspension before each atomization.Group A and Gro up B received the same amount of NS.After atomization 2 weeks?4 wee ks and 8 weeks,8 mice from each group were executed randomly, then take the left lung and spleen tissues within 24 hours spare in order to spare.To observe the airway remodeling by the lung tissue paraffin;to me asure the expression of TGF-?1, smad2, smad7 protein in the lung tissu e by immunohistochemical method;to Detected the percentage of Th17, CD4+CD25+ regulatory T cells in CD4+Tcells in the tissue of spleen by Flow cytometry instrument.Results:1.Compared with the group A,the mice in Group B and group C gradually irritability or Less dynamic Scratchi ng his nose?Difficulty breathing and so on in the excitation process.Thes e changes in group C than in group B have different degrees of mitigati on.2.The changes of group B and group C were higher than group A in the thickness of bronchial Total wall and smooth muscle(P<0.05).The cha nges of group C were mitigated than group B.They were significant after stimulate eight weeks(P<0.05).3.The number of Thl7 cells in group B and group C were both higher than in group A(P<0.05).The changes of group C were mitigated than group B.They were significant after stimulat e eight weeks(P<0.05).The number of CD4+CD25+Treg cells in group B and group C were both lower than in group A(P<0.05).The changes of group C were higher than group B.These changes were significant after stimulate eight weeks(P<0.05).4.the expression of smad2 protein in group B and group C were increased than in group A.The changes of group C were lower than group B.They were significant after stimulate eight weeks(P<0.05).The expression of smad7 protein in group B and group C were decreased than in group A.The changes of group C were higher than group B.They were significant after stimulate four weeks(P<0.05).An d were particularly significant after Stimulate eight weeks(P<0.01).The ex pression of TGF-?1 protein in group B and group C were increased than in group A.The changes of group C were lower than group B,They wer e significant after stimulate four weeks(P<0.05).And were particularly sign ificant after Stimulate eight weeks(P<0.01).5.The number of Th17 cells and the expression of smad2 and TGF-?1 protein were all positively cor related to airway remodeling.The number of CD4+CD25+ Treg cells and the expression of smad7 protein were both negatively correlated to airwa y remodeling.The number of Th17 cells was positively correlated to the expression of smad2 and TGF-?1 protein,and negatively correlated to the expression of smad7 protein. The number of CD4+CD25+Treg cells was negatively correlated to the expression of smad2 and TGF-?1 protein,and p ositively correlated to the expression of smad7 protein. Conclusion:1.The change of Airway remodeling in asthmatic mice is dynamic change proc ess.The airway remodeling of asthma will more serious with the extensio n of atomization firing time.The asthmatic airway remodeling mice indee d exist anomal changes of Th17cells,CD4+CD25+Treg, smads and TGF-?1 protien.With prolonged excitation increases,these changes were more obvi ous.2.Montelukastcan delay airway remodeling,with prolonged intervention the inhibition ofairway remodeling is more obvious.Montelukast can redu ce the number of Th17 cells and the expression of smad2 and TGF-?1 protein,increas the number of CD4+CD25+Treg cells and the expression of smad7 protein,adjust anomal changes of TGF-?/smads signaling pathways, improve the immunologic derangement of Th17/CD4+CD25+Treg in asthm atic mice.Thus delay the occurrence of airway remodeling and with prolo nged medicine increases,the changes were more obvious.