1,25(OH)_2D_3 could alleviate airway remodeling in model murine of chronic asthma

Objective To investigate the effects of 1,25(OH)2D3 on airway remodeling and the expression of matrix metalloprotease-9(MMP-9) in a murine model of chronic asthma,and to explore the potential mechanism of 1,25(OH)2D3 in the treatment of asthma.Methods BALB/c mice were sensitized and challenged with ovalbumin to establish the chronic asthmatic model.They were randomly divided into control group,asthma group,dexamethasone(DEX) group and VD group.The characteristic airway inflammation and alteration of airway structure were detected by HE staining.Morphometric analysis of the stained sections was performed using computerized image analysis system.The expression of MMP-9 in both activity and mRNA level was detected by gelatin zymograph and RT-PCR,respectively.Results(1)The infiltration of inflammatory cells,epithelial loss,smooth muscle cell layer thickening were decreased in DEX group and VD group when compared with those in asthma group(P0.05),but these changes were both more significant than those in the control group(P0.05);(2)WAm /Pbm、WAi/Pbm and N/Pbm decreased significantly in VD group when compared with those in asthma group(P0.05),but they were still higher than those in the control group(P0.05);(3)Stimulation with asthmatic serum induced a7.873-fold increase in the MMP-9 activity compared with that in the control group,and pretreatment with DEX or VD only induced a 2.238-fold or 3.460-fold increase in the MMP-9 activity compared with that in the control group(P0.05);(4) The mRNA level of MMP-9 in VD group(3.16±0.09) and DEX group(2.63±0.11) was decreased when compared with those in asthma group(5.74±0.13)(P0.05),but it was still higher than those in the control group(0.57±0.08)(P0.05).Conclusion Intervention with 1,25(OH)2D3 could markly alleviate the asthmatic airway remodeling and partly restore of appropriate structure of airway wall.It could also lower the expression of MMP-9 in the lung tissue on asthmatic condition,thus delay the process of airway remodeling.