Ziora D, Dworniczak S, Kozielski J
Department of Lung Diseases and Tuberculosis, Medical University of Silesia, Zabrze, Poland.
J Physiol Pharmacol. 2008 Dec;59 Suppl 6:809-17.
The aim of this study was to assess sputum levels of the metalloproteinases MMP-1, MMP-2, MMP-3, TIMP-1, and TIMP-2, as well as MMPs/TIMPs ratios in relation to exhaled NO (eNO) and sputum NOs (nitrates and nitrites) and IL8 obtained from chronic obstructive pulmonery disease (COPD) patients, healthy non-smokers, and healthy smokers. We found higher levels of TIMP-1 (118.9 ng/ml) and TIMP-2 (3.75 ng/ml) in COPD patients than in healthy smokers (17.7 ng/ml, P<0.03; 0.51 ng/ml, P>0.05, respectively) and healthy non-smokers (84.6 ng/ml, P>0.05; 1.61 ng/ml, P>0.05, respectively). We also observed significant positive correlations between concentrations of NOs and MMP-1, MMP-2, MMP-3, and TIMP-2 (r=0.37, P<0.02; r=0.60, P<0.0001; r=0.56, P<0.0004 and r=0.47 P<0.004, respectively) in COPD patients. IL8, MMP-2, MMP-3, and TIMP-2 levels in induced sputum were negatively correlated with airway obstruction, i.e., FEV(1)/FVC (r=-0.61, P<0.00009; r=-0.41, P<0.01; r=-0.38, P<0.02; r=-0.49, P<0.002). Our study points to a potentially pathogenic role of stromelysin-1 (MMP-3) in COPD.
本研究旨在评估慢性阻塞性肺疾病(COPD)患者、健康非吸烟者和健康吸烟者痰液中金属蛋白酶MMP-1、MMP-2、MMP-3、TIMP-1和TIMP-2的水平,以及MMPs/TIMPs比值与呼出一氧化氮(eNO)、痰液一氧化氮(硝酸盐和亚硝酸盐)和白细胞介素8(IL8)的关系。我们发现,COPD患者的TIMP-1(118.9 ng/ml)和TIMP-2(3.75 ng/ml)水平高于健康吸烟者(分别为17.7 ng/ml,P<0.03;0.51 ng/ml,P>0.05)和健康非吸烟者(分别为84.6 ng/ml,P>0.05;1.61 ng/ml,P>0.05)。我们还观察到,COPD患者中,一氧化氮浓度与MMP-1、MMP-2、MMP-3和TIMP-2之间存在显著正相关(r分别为0.37,P<0.02;r为0.60,P<0.0001;r为0.56,P<0.0004;r为0.47,P<0.004)。诱导痰液中的IL8、MMP-2、MMP-3和TIMP-2水平与气道阻塞呈负相关,即与FEV(1)/FVC呈负相关(r分别为-0.61,P<0.00009;r为-0.41,P<0.01;r为-0.38,P<0.02;r为-0.49,P<0.002)。我们的研究表明基质溶解素-1(MMP-3)在COPD中可能具有致病作用。