Beeh Kai Michael, Beier Jutta, Koppenhoefer Nicole, Buhl Roland
Pulmonary Department, Internal Medicine, University Hospital, Langenbeckstrasse 1, 55131 Mainz, Germany.
Chest. 2004 Oct;126(4):1116-22. doi: 10.1378/chest.126.4.1116.
Increased oxidant burden is involved in the pathogenesis of COPD. Glutathione (GSH) is a major antioxidant scavenging reactive oxygen and nitrogen species. We studied the concentrations of total and reduced GSH, glutathione disulfide (GSSG), and nitrosothiols in sputum supernatant of patients with COPD.
Twenty-five patients with moderate-to-severe COPD (FEV(1) 61 +/- 12% of predicted) and 25 healthy nonsmoking control subjects underwent sputum induction. Sputum total GSH and GSSG were measured spectrophotometrically, and nitrosothiols were quantified by enzyme assay. Exhaled nitric oxide (eNO) was also measured to correlate eNO with nitrosothiols in induced sputum.
Compared with healthy subjects, patients with COPD had increased sputum neutrophils (geometric mean, 65%; 95% confidence interval [CI], 57.5 to 71; vs 21%; 95% CI, 13.2 to 31.6; p < 0.001); total GSH (geometric mean, 7.1 micromol/L; 95% CI, 2.95 to 17; vs 5.1 micromol/L; 95% CI, 3.2 to 8.1; p = 0.024); GSSG (geometric mean, 4.1 micromol/L; 95% CI, 1.7 to 10; vs 0.84 micromol/L; 95% CI, 0.35 to 1.99; p = 0.002); and nitrosothiols (geometric mean, 60.4 micromol/L; 95% CI, 40 to 95.5; vs 38 micromol/L; 95% CI, 31.6 to 43.6; p = 0.04). Sputum GSSG was positively correlated with neutrophils (rho = 0.47, p = 0.016) and nitrosothiols (rho = 0.49, p = 0.024) in patients with COPD, whereas there was no correlation of eNO with nitrosothiols (rho = 0.38, p = 0.1).
Sputum concentrations of GSSG and nitrosothiols are increased in patients with COPD and associated with neutrophilic inflammation. These data underline the role of oxidative stress in the pathogenesis of COPD, and suggest that GSH is important to scavenge both reactive oxygen and nitrogen species.
氧化应激负担增加参与慢性阻塞性肺疾病（COPD）的发病机制。谷胱甘肽（GSH）是清除活性氧和氮物质的主要抗氧化剂。我们研究了COPD患者痰液上清液中总谷胱甘肽、还原型谷胱甘肽、谷胱甘肽二硫化物（GSSG）和亚硝基硫醇的浓度。
25例中重度COPD患者（FEV₁为预测值的61±12%）和25名健康非吸烟对照者接受痰液诱导。用分光光度法测量痰液总谷胱甘肽和GSSG，通过酶法对亚硝基硫醇进行定量。还测量了呼出一氧化氮（eNO），以将诱导痰液中的eNO与亚硝基硫醇进行关联。
与健康受试者相比，COPD患者痰液中性粒细胞增加（几何均值，65%；95%置信区间[CI]，57.5至71；vs 21%；95% CI，13.2至31.6；p<0.001）；总谷胱甘肽（几何均值，7.1μmol/L；95% CI，2.95至17；vs 5.1μmol/L；95% CI，3.2至8.1；p = 0.024）；GSSG（几何均值，4.1μmol/L；95% CI，1.7至10；vs 0.84μmol/L；95% CI，0.35至1.99；p = 0.002）；以及亚硝基硫醇（几何均值，60.4μmol/L；95% CI，40至95.5；vs 38μmol/L；95% CI，31.6至43.6；p = 0.04）。在COPD患者中，痰液GSSG与中性粒细胞呈正相关（rho = 0.47，p = 0.016），与亚硝基硫醇呈正相关（rho = 0.49，p = 0.024），而eNO与亚硝基硫醇无相关性（rho = 0.38，p = 0.1）。
COPD患者痰液中GSSG和亚硝基硫醇浓度增加，并与中性粒细胞炎症相关。这些数据强调了氧化应激在COPD发病机制中的作用，并表明谷胱甘肽对于清除活性氧和氮物质很重要。
