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慢性阻塞性肺疾病患者诱导痰金属蛋白酶及其抑制剂与呼出氮氧化物、痰一氧化氮及其他炎性细胞因子的关系

Induced sputum metalloproteinases and their inhibitors in relation to exhaled nitrogen oxide and sputum nitric oxides and other inflammatory cytokines in patients with chronic obstructive pulmonary disease.

作者信息

Ziora D, Dworniczak S, Kozielski J

机构信息

Department of Lung Diseases and Tuberculosis, Medical University of Silesia, Zabrze, Poland.

出版信息

J Physiol Pharmacol. 2008 Dec;59 Suppl 6:809-17.

PMID:19218708
Abstract

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.

摘要

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。

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