[慢性阻塞性肺疾病患者中环氧合酶-2和基质金属蛋白酶-2的表达与气流阻塞]

[Expressions of cyclooxygenase-2 and matrix metalloproteinase-2 and airflow obstruction in patients with chronic obstructive pulmonary disease].

作者信息

Chen Yan, Chen Ping

机构信息

Department of Respiratory Medicine, Second Xiangya Hospital, Central South University, Xiangya Medical School, Changsha 410011, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2005 May;28(5):324-7.

PMID:15949313

Abstract

OBJECTIVE

To investigate the expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2) in induced sputum and airway obstruction in patients with stable chronic obstructive pulmonary disease (COPD).

METHODS

Fifty-five patients with stable COPD and 10 age-matched controls were enrolled in the study. Sputum induction was collected by inhalation of 3% sodium chloride. Cell numbers and differentials in sputum suspension were counted with Wright's stain. The concentrations of prostaglandin E(2) (PGE(2)) and MMP-2 in sputum supernatant were measured by ELISA. COX-2 protein expression in the cells was detected by Western blot.

RESULTS

The total sputum cells, the numbers of alveolar macrophages (AM) and neutrophils (Neu) in COPD patients were significantly higher than those in the control group (P < 0.05 or P < 0.01). The number of AM and Neu was inversely correlated with FEV(1)%pred and FEV(1)/FVC (r = -0.280, P < 0.05, r = -0.345, P < 0.01; r = -0.677, r = -0.773, all P < 0.01). The level of COX-2 protein expression was higher in induced sputum in COPD patients than that in the control group. Concentrations of PGE(2) in the control group and in COPD patients with grade 0, I, IIA, IIB and III were (81 +/- 18), (111 +/- 17), (117 +/- 23), (118 +/- 29), (153 +/- 24), (194 +/- 28) ng/L, respectively. Concentrations of MMP-2 in the control group and in COPD patients with grade 0, I, IIA, IIB and III were (0.7 +/- 0.4), (4.0 +/- 0.9), (4.5 +/- 1.5), (7.7 +/- 3.1), (11.9 +/- 3.5), (18.5 +/- 5.0)microg/L, respectively. Concentrations of PGE(2) and MMP-2 in sputum in COPD patients were significantly higher than those in the control group (all P < 0.01). PGE(2) and MMP-2 were inversely correlated with FEV(1)%pred, FEV(1)/FVC in stable COPD patients (r = -0.748, r = -0.750, P < 0.01; r = -0.801, r = -0.816, all P < 0.01). Concentrations of PGE(2) were positively correlated with MMP-2 in COPD patients (r = 0.775, P < 0.01).

CONCLUSIONS

(1) There is chronic inflammatory process in airway of stable COPD. AM and Neu contribute to the process. (2) COX-2 and MMP-2 may be involved in the airway inflammatory process and contribute to airway remodeling in COPD.

摘要

目的

探讨环氧化酶-2（COX-2）和基质金属蛋白酶-2（MMP-2）在稳定期慢性阻塞性肺疾病（COPD）患者诱导痰中的表达及与气道阻塞的关系。

方法

选取55例稳定期COPD患者及10例年龄匹配的对照者纳入研究。通过吸入3%氯化钠诱导痰液。用瑞氏染色法对痰悬液中的细胞数量及分类进行计数。采用酶联免疫吸附测定法（ELISA）检测痰上清液中前列腺素E2（PGE2）和MMP-2的浓度。通过蛋白质印迹法检测细胞中COX-2蛋白的表达。

结果

COPD患者的总痰细胞数、肺泡巨噬细胞（AM）和中性粒细胞（Neu）数量均显著高于对照组（P<0.05或P<0.01）。AM和Neu数量与预测第一秒用力呼气容积（FEV1）%及FEV1/用力肺活量（FVC）呈负相关（r=-0.280，P<0.05，r=-0.345，P<0.01；r=-0.677，r=-0.773，均P<0.01）。COPD患者诱导痰中COX-2蛋白表达水平高于对照组。对照组及0级、Ⅰ级、ⅡA级、ⅡB级和Ⅲ级COPD患者痰中PGE2浓度分别为（81±18）、（111±17）、（117±23）、（118±29）、（153±24）、（194±28）ng/L。对照组及0级、Ⅰ级、ⅡA级、ⅡB级和Ⅲ级COPD患者痰中MMP-2浓度分别为（0.7±0.4）、（4.0±0.9）、（4.5±1.5）、（7.7±3.1）、（11.9±3.5）、（18.5±5.0）μg/L。COPD患者痰中PGE2和MMP-2浓度均显著高于对照组（均P<0.01）。稳定期COPD患者中，PGE2和MMP-2与预测FEV1%、FEV1/FVC呈负相关（r=-0.748，r=-0.750，P<0.01；r=-0.801，r=-0.816，均P<0.01）。COPD患者中，PGE2浓度与MMP-2呈正相关（r=0.775，P<0.01）。