慢性阻塞性肺疾病患者体内的内源性硫化氢

Endogenous hydrogen sulfide in patients with COPD.

作者信息

Chen Ya-Hong, Yao Wan-Zhen, Geng Bin, Ding Yan-Ling, Lu Ming, Zhao Ming-Wu, Tang Chao-Shu

机构信息

Respiratory Department, Peking University, Third Hospital, Beijing, ROC.

出版信息

Chest. 2005 Nov;128(5):3205-11. doi: 10.1378/chest.128.5.3205.

DOI:10.1378/chest.128.5.3205

PMID:16304263

Abstract

OBJECTIVES

COPD is characterized by progressive airway obstruction. Recent studies showed that besides nitric oxide (NO) and carbon monoxide (CO), endogenous hydrogen sulfide (H(2)S) might be the third signaling gasotransmitter. To clarify the role of endogenous H(2)S in the pathogenesis of COPD, we investigated the relation of serum H(2)S level to severity of COPD as defined by lung function and airway inflammation.

METHODS

Levels of serum H(2)S and NO, lung function, and cell differential counts in induced sputum were studied in 27 patients with acute exacerbation of COPD (AECOPD), 37 patients with stable COPD, and 13 healthy subjects. Patients with AECOPD had arterial blood gas levels measured and underwent Doppler echocardiography. In addition, in order to clarify the effects of age and smoking status on serum H(2)S level, we recruited three groups who were age matched to the study group but had no airflow limitation (59 subjects).

RESULTS

Serum H(2)S level (34.0 +/- 0.9 to 36.4 +/- 1.1 micromol/L [+/- SEM]) did not differ among healthy control subjects with different ages (56.6 to 75.0 years, respectively). Serum H(2)S level was significantly higher in patients with stable COPD than in patients with AECOPD and age-matched control subjects (p < 0.01) and correlated positively with NO level in all healthy control subjects and all patients with COPD (r = 0.352, p = 0.000). Serum H(2)S level was significantly lower in smokers than nonsmokers, both with AECOPD (p < 0.05) and healthy control subjects (p < 0.01). It was significantly lower in smokers with AECOPD than healthy smokers and smokers with stable COPD (p < 0.01). Serum H(2)S level differed and was decreased (p < 0.05) among stable COPD patients by stage of airway obstruction (p < 0.05), and it was lower in patients with stage III than stage I obstruction (p < 0.05). Serum H(2)S level in all patients with COPD and healthy control subjects correlated positively with the percentage of predicted FEV(1) value (r = 0.300, p = 0.009). It was lower in patients with AECOPD and systolic pulmonary artery pressure (PASP) > or = 35 mm Hg than those with PASP within the normal range (< 35 mm Hg) [p < 0.05] and was negatively correlated with PASP (r = - 0.561, p = 0.011). Serum H(2)S level was negatively correlated with proportion of neutrophils in sputum (r = - 0.422, p = 0.001) and positively correlated with proportion of lymphocytes (r = 0.286, p = 0.028) and macrophages (r = 0.334, p = 0.01) in all patients with COPD.

CONCLUSIONS

Endogenous H(2)S is involved in the pathogenesis of airway obstruction in COPD, and its alteration in level may be connected with disease activity and severity.

摘要

目的

慢性阻塞性肺疾病（COPD）的特征为进行性气道阻塞。近期研究表明，除一氧化氮（NO）和一氧化碳（CO）外，内源性硫化氢（H₂S）可能是第三种信号气体递质。为阐明内源性H₂S在COPD发病机制中的作用，我们研究了血清H₂S水平与根据肺功能和气道炎症定义的COPD严重程度之间的关系。

方法

对27例慢性阻塞性肺疾病急性加重期（AECOPD）患者、37例稳定期COPD患者和13名健康受试者的血清H₂S和NO水平、肺功能及诱导痰中的细胞分类计数进行了研究。AECOPD患者检测了动脉血气水平并接受了多普勒超声心动图检查。此外，为阐明年龄和吸烟状态对血清H₂S水平的影响，我们招募了三组与研究组年龄匹配但无气流受限的人群（59名受试者）。

结果

不同年龄（分别为56.6至75.0岁）的健康对照受试者血清H₂S水平（34.0±0.9至36.4±1.1微摩尔/升[±标准误]）无差异。稳定期COPD患者的血清H₂S水平显著高于AECOPD患者和年龄匹配的对照受试者（p<0.01），且在所有健康对照受试者和所有COPD患者中与NO水平呈正相关（r=0.352，p=0.000）。吸烟者的血清H₂S水平显著低于非吸烟者，AECOPD患者（p<0.05）和健康对照受试者（p<0.01）均如此。AECOPD吸烟者的血清H₂S水平显著低于健康吸烟者和稳定期COPD吸烟者（p<0.01）。稳定期COPD患者的血清H₂S水平因气道阻塞阶段而异且降低（p<0.05），III期患者低于I期阻塞患者（p<0.05）。所有COPD患者和健康对照受试者的血清H₂S水平与预计FEV₁值百分比呈正相关（r=0.300，p=0.009）。AECOPD且收缩期肺动脉压（PASP）≥35 mmHg的患者血清H₂S水平低于PASP在正常范围内（<35 mmHg）的患者[p<0.05]，且与PASP呈负相关（r=-0.561，p=0.011）。所有COPD患者的血清H₂S水平与痰中中性粒细胞比例呈负相关（r=-0.422，p=0.001），与淋巴细胞比例（r=0.286，p=0.028）和巨噬细胞比例（r=0.334，p=0.01）呈正相关。