Background Aerobic exercise can improve symptoms,reduce airway inflammation,and even ameliorate airway remodeling in asthmatic animals and patients.However,previous studies have focused mainly on the effect of aerobic...Background Aerobic exercise can improve symptoms,reduce airway inflammation,and even ameliorate airway remodeling in asthmatic animals and patients.However,previous studies have focused mainly on the effect of aerobic exercise on steroid-sensitive asthma （SSA）.The goals of this study were to determine the effect of low-intensity aerobic exercise training on airway hyperresponsiveness,inflammation,and remodeling in a rat model of steroid-resistant asthma （SRA） and to identify the potential mechanisms underlying these effects.Methods Endotoxin-free ovalbumin with or without lipopolysaccharide were applied to establish rat models of SRA and SSA,respectively.Airway hyperresponsiveness,inflammation,remodeling,expression of interleukin （IL）-25,IL-33,thymic stromal lymphopoietin （TSLP）,high mobility group box-1 （HMGB1）,and IL-17 in bronchoalveolar lavage fluid （BALF）,and the role of dexamethasone （DXM） were compared between these two asthmatic rat models.The effect of low-intensity aerobic exercise training and anti-HMGB1 treatment on airway hyperresponsiveness,inflammation,and remodeling in SRA rats also was evaluated.Results SRA rats developed neutrophil-dominated airway inflammation （（29.5±4.1）％ of the total cell numbers in BALF）,whereas SSA rats developed eosinophil-dominated airway inflammation （（24.0±6.1）％ of the total cell numbers in BALF）.Compared with SSA rats,SRA rats had more severe airway hyperresponsiveness,lower levels of IL-25 （（33.6±10.3） vs.（104.8±24.9） pg/ml）,IL-33 （（87.5±25.0） vs.（226.6±40.7） pg/ml）,and TSLP （（1 933.2±899.5） vs.（7 224.0±992.1） pg/ml）,and higher levels of HMGB1 （（21.2±4.5） vs.（5.4±1.6） ng/ml） and IL-17 （（780.5±261.7） vs.（291.4±76.4） pg/ml） in BALF （all P ＜0.05）.However,there was no significant difference in goblet cell hyperplasia,subepithelial collagen thickness,and airway smooth muscle remodeling between the two groups.Compared with control SSA rats,airway hyp展开更多
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81070026）, the Key Project of Hunan Provincial Science and Technology Department （No. 2012FJ4375）, and the Open Innovation Platform of Hunan College （No. 10K076）.
文摘Background Aerobic exercise can improve symptoms,reduce airway inflammation,and even ameliorate airway remodeling in asthmatic animals and patients.However,previous studies have focused mainly on the effect of aerobic exercise on steroid-sensitive asthma （SSA）.The goals of this study were to determine the effect of low-intensity aerobic exercise training on airway hyperresponsiveness,inflammation,and remodeling in a rat model of steroid-resistant asthma （SRA） and to identify the potential mechanisms underlying these effects.Methods Endotoxin-free ovalbumin with or without lipopolysaccharide were applied to establish rat models of SRA and SSA,respectively.Airway hyperresponsiveness,inflammation,remodeling,expression of interleukin （IL）-25,IL-33,thymic stromal lymphopoietin （TSLP）,high mobility group box-1 （HMGB1）,and IL-17 in bronchoalveolar lavage fluid （BALF）,and the role of dexamethasone （DXM） were compared between these two asthmatic rat models.The effect of low-intensity aerobic exercise training and anti-HMGB1 treatment on airway hyperresponsiveness,inflammation,and remodeling in SRA rats also was evaluated.Results SRA rats developed neutrophil-dominated airway inflammation （（29.5±4.1）％ of the total cell numbers in BALF）,whereas SSA rats developed eosinophil-dominated airway inflammation （（24.0±6.1）％ of the total cell numbers in BALF）.Compared with SSA rats,SRA rats had more severe airway hyperresponsiveness,lower levels of IL-25 （（33.6±10.3） vs.（104.8±24.9） pg/ml）,IL-33 （（87.5±25.0） vs.（226.6±40.7） pg/ml）,and TSLP （（1 933.2±899.5） vs.（7 224.0±992.1） pg/ml）,and higher levels of HMGB1 （（21.2±4.5） vs.（5.4±1.6） ng/ml） and IL-17 （（780.5±261.7） vs.（291.4±76.4） pg/ml） in BALF （all P ＜0.05）.However,there was no significant difference in goblet cell hyperplasia,subepithelial collagen thickness,and airway smooth muscle remodeling between the two groups.Compared with control SSA rats,airway hyp
