Role of MMP/TIMP and interfering effects of eorticosteroid treatment in pathogenesis of bronchial asthma
NING Fang-yu, WANG Xiao-zhi
Published 2008-12-20
Cite as Int J Respir, 2008,28(24): 1478-1481,封3. DOI: 10.3760/cma.j.issn.1673-436x.2008.24.002
Abstract
Objective To investigate the correlations between MMP,TIMP and airway remodeling in brochial asthma(asthma),and the effect of preventive inhaling budesonide(BUD)on airway remodeling.Methods Seventy-two Wistar rats were divided into control group,asthmatic group(sensitized by OVA)and steroids treated group(treated by steroid and sensitized by OVA),each group had 24 rats.The subjects were observed at 3 phases:7 days,28 days,35 days after activation.General histological changes wereobserved using HE and Masson trichrome stained sections.The parameter of the internal perimeter(Pi),bronchial smooth muscle area(Wam),internal wall area(Wai),and Wc01 collage deposition(Wcol)of the airway were measured by computer-assisted image analysis system.The protein expressions of MMP-9 and TIMP-1 in lung tissue were examined by immunohistochemical analysis and the concentrations of MMP-9 and TIMP-1 in the blood and BALF were quantified by ELISA.Results ①The Wai/Pi,Wam/Pi and Wcol/Pi of asthmatic group in 28 days and 35 days were significantly higher than those of control group(P<0.05 or P<0.01);After treatment with BUD the Wam/Pi of 28 days and 35 days BUD treated group had no significant diference with that of corresponding asthmatic group;but the Wcol/Pi of 28 days and 35 days BUD treated group decreased obviously compared with that of asthmatic group(P<0.01).The Wai/Pi of 35 days BUD treated group was significantly lower than that of the 35 days asthmatic group(P<0.05),but was significantly higher than the 35 days control group(P<0.05).②MMP-9 and MMP-9/TIMP-1 increased at the time point of 7 days.but it decreased in the late stage(35 days)of airway remodeling in asthmatic group.And the level of TIMP-1 increased at the time point of 7 days and had a downward trend at the time point of 35 days.After treatment with BUD,MMP-9,TIMP-1 and MMP-9/TIMP-1 increased at the time point of 7 days.but there was no statistic significance between asthmatic group and BUD group in the late stage(35 days).Conclusions The inbalance of MMP-9/TIMP-1 ratios may exist in the progress of asthma.Regulating the balance between MMP-9 and TIMP-1 by steroids may be one of the mechanisms by which airway inflammation and remodeling are inhibited in asthma.
Key words:
Bronchial asthma; MMP-9; TIMP-1; Corticosteroid
Contributor Information
NING Fang-yu
Department of Respiratory Medicine,the Affiliated Hospital of Binzhou Medical College,Binzhou 256603,China
WANG Xiao-zhi
Department of Respiratory Medicine,the Affiliated Hospital of Binzhou Medical College,Binzhou 256603,China