内源性硫化氢在慢性阻塞性肺疾病患者中的变化及意义

目的研究内源性硫化氢(H2S)在慢性阻塞性肺疾病(COPD)发病中的作用。方法COPD急性加重组(AECOPD组)27例、稳定期COPD组37例和健康对照组13名,在入选时测定血清H2S和一氧化氮(NO)水平、肺功能、诱导痰细胞分类计数,对AECOPD患者行超声心动图和血气分析。结果(1)血清H2S水平稳定期COPD组[(50·8±2·5)μmol/L]比健康对照组[(39·8±1·6)μmol/L]、AECOPD组[(33·5±2·2)μmol/L]均显著增加(P均<0·01)。(2)AECOPD组吸烟者血清H2S[(28·1±1·3)μmol/L]比非吸烟者[(39·4±3·9)μmol/L,P<0·05]和健康非吸烟者显著降低[(39·8±1·6)μmol/L,P<0·01]。(3)稳定期COPD组不同程度气流阻塞患者血清H2S水平呈线性下降趋势(P<0·05),COPD全球创议(GOLD)Ⅲ期[(45·1±4·1)μmol/L]较Ⅰ期患者[(70·2±6·2)μmol/L]血清H2S水平显著下降(P<0·05)。(4)AECOPD组伴有肺动脉高压患者血清H2S水平显著降低[(26·3±2·2)、(36·2±2·5)μmol/L,P<0·05]。(5)血清H2S与NO、第一秒用力呼气容积占预计值百分比(FEV1占预计值%)、诱导痰淋巴细胞计数、诱导痰巨噬细胞计数均呈正相关(r=0·278~0·533,P均<0·05或0·01),与肺动脉收缩压(PASP)、诱导痰中性粒细胞计数均呈负相关(r=-0·561、-0·422,P=0·011、0·001)。结论内源性H2S可能参与COPD气流阻塞的发病,作为一种无创指标监测疾病严重程度和活动度具有一定意义。

Endogenous hydrogen sulfide in patients with chronic obstructive pulmonary disease

OBJECTIVE: To investigate the role of endogenous hydrogen sulfide (H(2)S) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Levels of serum H(2)S and nitric oxide (NO), lung function and cell differential count in induced sputum were studied in 27 patients with acute exacerbation of COPD (AECOPD), 37 patients with stable COPD and 13 health subjects. Echo-Doppler assessment and arterial blood gas were measured in patients with AECOPD. RESULTS: (1) The serum H(2)S level was significantly higher in patients with stable COPD [(50.8 +/- 2.5) micromol/L] as compared to those in the controls [(39.8 +/- 1.6) micromol/L] and in patients with AECOPD [(33.5 +/- 2.2) micromol/L, P < 0.01]. (2) The level of serum H(2)S was significantly lower in smokers with AECOPD [(28.1 +/- 1.3) micromol/L] as compared to nonsmokers with AECOPD [(39.4 +/- 3.9) micromol/L, P < 0.05] and healthy nonsmokers [(39.8 +/- 1.6) micromol/L, P < 0.01]. (3) There was significant difference in the serum H(2)S level among stable COPD patients with different severity of airway obstruction (P < 0.05); being lower in patients with stage III [(45.1 +/- 4.1) micromol/L] as compared to stage I obstruction [(70.2 +/- 6.2) micromol/L, P < 0.05]. (4) AECOPD with pulmonary hypertension pulmonary artery systolic pressure (PASP) > or = 35 mm Hg (1 mm Hg = 0.133 kPa) showed a lower serum H(2)S level [(26.3 +/- 2.2), (36.2 +/- 2.5) micromol/L, P < 0.05] than that with a normal resting PASP. (5) H(2)S in serum was positively correlated with NO levels (r = 0.278, P = 0.029), FEV(1)% predicted values (r = 0.533, P = 0.000), percentage of sputum lymphocytes (r = 0.286, P = 0.028) and macrophages (r = 0.334, P = 0.01); and negatively correlated with PASP (r = -0.561, P = 0.011) and the percentage of sputum neutrophils (r = -0.422, P = 0.001) in patients with COPD. CONCLUSION: Endogenous H(2)S may be involved in the pathogenesis of airway obstruction in COPD and may be a noninvasive marker of disease activity and severity.