慢性阻塞性肺疾病患者氧化应激与血清基质金属蛋白酶9的关系及其在并发肺动脉高压中的作用

The relationship between oxidative stress and serum matrix metalloproteinase-9 in chronic obstructive pulmonary disease with pulmonary hypertension

目的 研究慢性阻塞性肺疾病（COPD）患者氧化应激与血清基质金属蛋白酶9（MMP-9）的关系及其在并发肺动脉高压（PAH）中的作用.方法 对62例COPD患者采用多普勒超声心动仪测定肺动脉收缩压（PASP）,按PASP将患者分为单纯COPD组（PASP正常）、轻度PAH组、中度PAH组、重度PAH组;同期另择体检健康者19例作为对照组.采用ELISA法检测并比较各组研究对象尿8-异前列腺素F2α（8-iso-PGF2α）和血清MMP-9水平,分析COPD并发PAH者尿8-iso-PGF2α水平与血清MMP-9水平的相关性.结果 中度PAH组及重度PAH组尿8-iso-PGF2α及血清MMP-9水平均明显高于对照组、单纯COPD组及轻度PAH组（均P＜0.05）,轻度PAH组MMP-9水平明显高于对照组（P＜0.05）,各组间其他两两比较均无明显差异（均P＞0.05）.相关性分析结果显示,COPD并发PAH者,尿8-iso-PGF2α水平与血清MMP-9水平呈显著正相关[r=0.372,P=0.009）.结论 COPD患者尿8-iso-PGF2α和血清MMP-9水平升高与并发中-重度PAH密切相关,通过影响肺血管重建起作用;COPD患者氧化应激增加可促使MMP-9合成和分泌.

Objective To investigate the relationship between oxidative stress and serum matrix metalloproteinase-9 （MMP-9） in chronic obstructive pulmonary disease （COPD） with pulmonary hypertension （PAH）. Method Doppler ultrasound cardioechography was performed to detect the pulmonary arterial systolic pressure （PASP） in 62 patients with COPD who were divided into simple COPD group, mild PAH group, moderate PAH group and severe PAH group. Nineteen healthy subjects were selected as control group. Enzyme linked immunosorbent assay（ELISA） was performed to detect urinary 8-isoprostaglandin F2 a （8-iso-PGF2a）and serum MMP-9. Results The levels of urinary 8-iso-PGF2a in severe PAH group [（19.95±3.92）pg/mg creatinine] and in moderate PAH group [（13.07 ± 4.35）pg/mg creatinine]were higher than those in mild PAH group [（ 7.69 ± 3.81 } pg/mg creatinine], simple COPD group[（ 5.66 ± 2.12 μg/mg creatinine] and control group of[（ 6.25 ± 1.79 ）pg/mg creatinine]（ P〈0. 05）. The levels of serum MMP-9 in severe PAH group[（3.24± 0.81 ） μ g/L]and in moderate PAH group[（3.22 ± 1.02} μg/L] were higher than those in mild PAH group[（2.51 ± 0.62） μ g/L], simple COPD group[（2.37 ± 0.7 ） μg/L]and control group[（2.08 ± 0.59） μ g/LJ（P〈0.05）. The level of serum MMP-9 in mild PAH group was higher than that in control group （P〈0.05 ）. The levels of urinary 8-iso-PGF2 a were correlated with the levels of serum MMP-9 positively（r=0.372,P〈0.05 ）, and there was a correlation between levels of urinary 8-iso-PGF2 a and cigarette using index （r=0.410,P〈0.05）. Conclusion High-level urinary 8-iso-PGF2 a and seum MMP-9 are closely correlated with moderate PAH and severe PAH in patients with COPD,which is associated with pneumoangiogram remodeling. Increased oxidative stress may augment synthesis and externalization of MMP-9 in patient with COPD.