慢性阻塞性肺疾病患者环氧合酶2和基质金属蛋白酶2的表达及其与气流阻塞的关系

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

目的探讨慢性阻塞性肺疾病(COPD)患者诱导痰中环氧合酶2(COX-2)及基质金属蛋白酶2(MMP-2)的表达及其与气流阻塞的关系。方法COPD组55例(COPD稳定期患者,其中0级12例、Ⅰ级10例、ⅡA级12例、ⅡB级11例和Ⅲ级10例)和正常对照组10名行痰诱导,对痰悬液进行细胞分类计数,应用酶联免疫吸附测定(ELISA)法检测诱导痰上清液中前列腺素E2(PGE2)和MMP2浓度,Westernblot法测定诱导痰细胞中COX-2蛋白表达。结果(1)COPD组诱导痰中细胞总数、肺泡巨噬细胞(AM)数和中性粒细胞(Neu)数较正常对照组显著增高(P<0.05或P<0.01)。AM、Neu与第一秒用力呼气容积占预计值%(FEV1占预计值%)、一秒率(FEV1/FVC)分别呈负相关(r=-0.280、P<0.05,r=-0.345、P<0.01;r=-0.677,r=-0.773,P均<0.01)。(2)Westernblot显示COPD组患者诱导痰细胞中COX-2蛋白表达(57±8)显著高于正常对照组(83±10,P<0.05)。(3)COPD各组诱导痰PGE2浓度[分别为(111±17)、(117±23)、(118±29)、(153±24)、(194±28)ng/L]显著高于正常对照组[(81±18)ng/L,P均<0.01],且与FEV1占预计值%、FEV-1/FVC呈负相关(r=-0.748,r=-0.750,P均<0.01),与MMP-2浓度呈正相关(r=0.775,P<0.01)。COPD各组诱导痰MMP2浓度[(4.0±0.9)、(4.5±1.5)、(7.7±3.1)、(11.9±3.5)、(18.5±5.

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)μg/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. utetoairwayremodelinginCOPD. Keywords】 Pulmonarydisease,c