a Department of Respiratory Medicine , The Affiliated Hospital of Yan'an University , Yan'an , People's Republic of China.
b Department of Respiratory and Critical Care Medicine , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , People's Republic of China.
Immunopharmacol Immunotoxicol. 2019 Apr;41(2):224-230. doi: 10.1080/08923973.2019.1609496. Epub 2019 May 3.
The aim of this work was to compare matrix metalloproteinase-9 and -12, tissue inhibitor of metalloproteinase-1 and -4, and neutrophil elastase in exhaled breath condensate (EBC) and peripheral blood of patients with COPD. Peripheral blood and EBC samples from COPD patients and healthy donors were collected. In serum and EBC, MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 proteins were detected by ELISA. The mRNA expression levels of MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 in peripheral blood mononuclear cells (PBMCs) were analyzed by qRT-PCR. The protein levels of MMP-9 (=.034) and MMP-12 (=.041) in the EBC of COPD smokers were higher than those of COPD never-smokers. The concentrations of TIMP-1 (=.072) and TIMP-4 (=.084) in the EBC of COPD smokers were higher than those of COPD never-smokers; however, the difference was not statistically significant. MMP-9 (=-0.78, <.0001) and TIMP-1 (=-0.71, <.0001) levels in EBC were significantly negatively correlated with pulmonary function FEV%pred. The protein levels of MMP-12 (=-0.37, =.034) and TIMP-4 (=-0.34, =.041) were also negatively correlated with FEV1%pred. The expression of MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 in PBMCs and serum of COPD smokers were significantly higher than those of control never-smokers (<.05). Exhaled MMP-9, MMP-12, TIMP-1, and TIMP-4 levels increased in stable COPD patients and were negatively correlated with FEV1%pred, which suggests the usefulness of their measurement in EBC for the monitoring of airway inflammation. However, to better assess their diagnostic or prognostic value, larger studies are necessary.
本研究旨在比较基质金属蛋白酶-9 和 -12、金属蛋白酶组织抑制剂-1 和 -4 以及中性粒细胞弹性蛋白酶在慢性阻塞性肺疾病（COPD）患者的呼出气冷凝物（EBC）和外周血中的水平。收集 COPD 患者和健康供体的外周血和 EBC 样本。通过 ELISA 检测血清和 EBC 中的 MMP-9、MMP-12、NE、TIMP-1 和 TIMP-4 蛋白。通过 qRT-PCR 分析外周血单个核细胞（PBMC）中 MMP-9、MMP-12、NE、TIMP-1 和 TIMP-4 的 mRNA 表达水平。COPD 吸烟者的 EBC 中 MMP-9（=.034）和 MMP-12（=.041）的蛋白水平高于 COPD 不吸烟者。EBC 中 TIMP-1（=.072）和 TIMP-4（=.084）的浓度高于 COPD 不吸烟者，但差异无统计学意义。EBC 中 MMP-9（=-0.78，<.0001）和 TIMP-1（=-0.71，<.0001）水平与肺功能 FEV%pred 呈显著负相关。EBC 中 MMP-12（=-0.37，=.034）和 TIMP-4（=-0.34，=.041）的蛋白水平也与 FEV1%pred 呈负相关。COPD 吸烟者 PBMC 和血清中 MMP-9、MMP-12、NE、TIMP-1 和 TIMP-4 的表达明显高于对照组不吸烟者（<.05）。稳定期 COPD 患者的呼出气 MMP-9、MMP-12、TIMP-1 和 TIMP-4 水平升高，与 FEV1%pred 呈负相关，这提示其在 EBC 中的测量可用于监测气道炎症。然而，为了更好地评估其诊断或预后价值，需要进行更大规模的研究。
