EFFECTS OF N-ACETYLCYSTEIN AND OTHER AGENTS ON THE ROLE OF MATRIX METALLOPROTEINASES IN AIRWAY REMODELLING OF COPD RAT MODELS / 解放军医学杂志

ABSTRACT

Fifty three Wistar rats were randomly divided into healthy control group, COPD model group and NAC group, PKC inhibitor H7 intervention group and TGF ? monocolonal antibody group(TGF ? MA group).To study the role of matrix metalloproteinases(MMPs) and the tissue inhibitor of MMPs(TIMP 1) in the airway extracellular matrix(ECM) remodelling of COPD rat models and to observe the effects of NAC, H7 and TGF ? MA intervention on the regulation of MMPs and TIMP 1 and on ECM remodelling of the airway walls. Compared with control group, the airway collagen, the hydroxyproline(Hy) content of lung homogenates ,the number of fibroblasts(Fb) , the protein and/or mRNA expressions of MMP 2, MMP 9, TIMP 1 and TGF ? Ⅰ, Ⅱ receptor and the enzyme activities of MMP 2 (72kD), MMP 9 (92kD) were significantly increased in COPD model group. In all the drug intervention groups, the expressions of the above parameters were significantly decreased than those in model group except for Hy and Fb in H7 group, protein expression of TGF ? I receptor in NAC group and MMP 9 in TGF ? MA group. The results suggested that increased MMPs as matrix degrading enzymes might be responsible for the excessive degradation of ECM in airway, whereas incresed TIMPs might promote excessive ECM synthesis and deposition. The imbalance of MMP 9/TIMP 1 was related to the airway ECM remodelling. An antioxidant NAC and TGF ? MA might regulate the MMPs/TIMP 1 expression and reduce the airway fibrosis.H7 had strong collagenase inhibitory action,resulting increse in Hy and Fbs. The data may be helpful for searching effective prevention and treatment of airway ECM remodelling.