[健康吸烟者诱导痰中气道重塑的标志物]

[Markers of airway remodeling in induced sputum from healthy smokers].

作者信息

Avilés B, Belda J, Margarit G, Bellido-Casado J, Martínez-Brú C, Casan P

机构信息

Departamento de Neumología, Hospital de la Santa Creu i de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España.

出版信息

Arch Bronconeumol. 2006 May;42(5):235-40. doi: 10.1016/s1579-2129(06)60452-7.

DOI:10.1016/s1579-2129(06)60452-7

PMID:16740239

Abstract

OBJECTIVE

Airway remodeling in chronic obstructive pulmonary disease (COPD) has been linked to the equilibrium between matrix metalloproteinase (MMP) 9 and its inhibitor, tissue inhibitor of metalloproteinase (TIMP) 1. However, that equilibrium has not been analyzed in healthy smokers. The aim of this study was to assess the equilibrium between MMP-9 and TIMP-1 in induced sputum from healthy smokers, healthy nonsmokers (controls), and patients with COPD.

PATIENTS AND METHODS

Samples of induced sputum were obtained from 35 individuals: 12 healthy smokers, 12 controls, and 11 patients with COPD. In each sample, a differential cell count was performed and enzyme-linked immunosorbent assays were used to analyze the concentrations of MMP-9 (total and active fraction) and TIMP-1.

RESULTS

Compared with controls, healthy smokers were found to have a higher mean (SD) concentration of total MMP-9 (273 [277] ng/mL vs 128 [146] ng/mL) and a higher ratio of total MMP-9 to TIMP-1 (0.16 [0.14] vs 0.08 [0.06]). However, the ratio of active MMP-9 to TIMP-1 was similar in the 2 groups. Samples from patients with COPD had the highest concentrations of total MMP-9 (477 [262] ng/mL) and active MMP-9 (178 [126] ng/mL) and the lowest concentrations of TIMP-1 (1.044 [1.036] microg/mL). When all groups were considered together, there was an inverse relationship between the MMP-9/TIMP-1 ratio and the forced expiratory volume in the first second (FEV1). The relationship between the active MMP-9/TIMP-1 ratio and FEV1 was even stronger, and the relation of both ratios with FEV1 became stronger still when smoking was considered.

CONCLUSIONS

Healthy smokers had a higher concentration of total MMP-9 and that concentration was correlated with their exposure to tobacco smoke. Maintenance of the active MMP-9/TIMP-1 ratio in healthy smokers may explain the absence of progressive airway obstruction. Measurement of active MMP-9 concentration could be useful for assessment of airway remodeling.

摘要

目的

慢性阻塞性肺疾病（COPD）中的气道重塑与基质金属蛋白酶（MMP）9及其抑制剂金属蛋白酶组织抑制剂（TIMP）1之间的平衡有关。然而，尚未对健康吸烟者中的这种平衡进行分析。本研究的目的是评估健康吸烟者、健康非吸烟者（对照组）和COPD患者诱导痰中MMP - 9和TIMP - 1之间的平衡。

患者和方法

从35名个体中获取诱导痰样本：12名健康吸烟者、12名对照者和11名COPD患者。对每个样本进行细胞分类计数，并使用酶联免疫吸附测定法分析MMP - 9（总浓度和活性部分）和TIMP - 1的浓度。

结果

与对照组相比，发现健康吸烟者的总MMP - 9平均（标准差）浓度更高（273 [277] ng/mL对128 [146] ng/mL），总MMP - 9与TIMP - 1的比率更高（0.16 [0.14]对0.08 [0.06]）。然而，两组中活性MMP - 9与TIMP - 1的比率相似。COPD患者的样本中总MMP - 9（477 [262] ng/mL）和活性MMP - 9（178 [126] ng/mL）浓度最高，TIMP - 1浓度最低（1.044 [1.036] μg/mL）。当将所有组一起考虑时，MMP - 9/TIMP - 1比率与第一秒用力呼气量（FEV1）之间存在负相关。活性MMP - 9/TIMP - 1比率与FEV1之间的关系更强，并且当考虑吸烟因素时，两个比率与FEV1的关系变得更强。