慢性阻塞性肺疾病患者诱导痰基质金属蛋白酶及其抑制剂与气道炎性反应及气道重塑的关系

目的检测慢性阻塞性肺疾病（COPD）、健康吸烟者及非吸烟者诱导痰上清液MMP-9、TIMP-1的浓度，分析MMP-9、TIMP-1的变化与气道重塑的关系。方法采用双抗夹心酶联免疫吸附试验法检测COPD组46例、吸烟组42例和非吸烟组40例受试者诱导痰上清液MMP-9、TIMP-1的浓度。结果COPD组诱导痰MMP-9浓度（782．2±328．4）ng／ml，高于吸烟组（362．6±210．2）ng／ml（P〈0．01），高于非吸烟组（126．4±110．2）ng／ml（P〈0．01）。COPD组MMP-9／TIMP-1比值0．7±0．6低于吸烟组1．6±1．1（P〈0．05）和非吸烟组1．5±1．3（P〈0．05），吸烟组和非吸烟组无统计学差异（P〉0．05）。COPD组MMP-9浓度与COPD严重程度呈正相关，吸烟组MMP-9浓度与吸烟年盒数呈正相关。结论在COPD发病中存在MMP-9／TIMP-1失衡。MMP-9／TIMP-1保持平衡或许可解释吸烟却不引起慢性气流受限。

Metallopreteinaes-9/tissue inhibitor of metalloproteinase-1 in induced sputum in patients with chronic obstructive pulmonary disease and their relationship to airway inflammation and Airway Remodeling

Objective To investigate the levels of metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1） in induced sputum in patients with chronic obstructive pulmonary disease （ COPD）, and its relationship of them to sairway inflammation and Airway Remodeling. Methods Sputum supernatants of 46 in-patients with CO＇PDand 42 healthy smokers and 40 healthy controls were analyzed. Sputum supernatant concentration of MMP-9 and TIMP-1 were measured through enzyme-linked immunosorbent assay （ELISA）. Results The sputum supernatant concentration of MMP-9 of COPD was higher than that of the healthy smokers （P 〈 0.01 ） and healthy controls （P 〈 0.01 ）. The ratio of MMP-9/TIMP- 1 of COPD was lower than that of the other groups. The ratio of MMP-9/TIMP-1 in the healthy smokers （P 〈 0. 05 ） and healthy controls did not show significant difference （P 〉 0.05 ）. The sputum supernatant concentration of MMP-9 in induced sputum of COPD patients was positively correlated with the COPD severity. The concentration of the MMP-9 in healthy smokers was also correlated with the extent of smoking habit. Conclusions An imbalance between MMP-9 and TIMP-1 in induced sputum in COPD is associated with airway inflammation and remodeling. Maintenance of the MMP-9/TIMP-1 ratio in healthy smokers may explain the absence of progressive airway obstruction.