Sun Yun, Wang Keyi, Li Min-Xia, He Wei, Chang Jin-Rui, Liao Cheng-Cheng, Lin Fan, Qi Yong-Fen, Wang Rui, Chen Ya-Hong
Pulmonary and Critical Care Medicine Department, Peking University Third Hospital, Beijing 100191, China.
Department of Thoracic Surgery, Peking University Third Hospital, Beijing 100191, China.
Sci Rep. 2015 Oct 12;5:14971. doi: 10.1038/srep14971.
Oxidative stress and inflammation play crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Most patients with COPD show a poor response to corticosteroids. Hydrogen sulfide (H2S ) has been implicated in the pathogenesis of COPD, but its expression and effects in lung tissue from COPD patients are not clear. In peripheral lung tissue samples from 24 patients, we found that compared with nonsmokers, the protein level of cystathionine-γ-lyase (CSE) was decreased in smokers and COPD patients. CSE mRNA increased but cystathionine-β-synthase (CBS) mRNA decreased in COPD patients. H2S donors increased glutathione and superoxide dismutase in CS exposed U937 cells and inhibited CS-induced TNF-α and IL-8 secretion. Dexamethasone alone had no effect on lipopolysaccharide (LPS) induced TNF-α release by alveolar macrophages from CS exposed rats, however the combination of dexamethasone and H2S donor significantly inhibited TNF-α release. Thus, H2S metabolism is altered in lung tissue of smokers and COPD patients. Supplementation of H2S protects against CS-induced oxidative stress and inflammation in macrophages and H2S on steroid sensitivity deserves further investigation.
氧化应激和炎症在慢性阻塞性肺疾病(COPD)的发病机制中起关键作用。大多数COPD患者对皮质类固醇反应不佳。硫化氢(H2S)与COPD的发病机制有关,但其在COPD患者肺组织中的表达及作用尚不清楚。在24例患者的外周肺组织样本中,我们发现与非吸烟者相比,吸烟者和COPD患者中胱硫醚-γ-裂解酶(CSE)的蛋白水平降低。COPD患者中CSE mRNA增加而胱硫醚-β-合酶(CBS)mRNA减少。H2S供体增加了暴露于香烟烟雾提取物(CS)的U937细胞中的谷胱甘肽和超氧化物歧化酶,并抑制了CS诱导的肿瘤坏死因子-α(TNF-α)和白细胞介素-8(IL-8)分泌。单独使用地塞米松对暴露于CS的大鼠肺泡巨噬细胞脂多糖(LPS)诱导的TNF-α释放没有影响,然而地塞米松和H2S供体的联合使用显著抑制了TNF-α释放。因此,吸烟者和COPD患者肺组织中H2S代谢发生改变。补充H2S可防止CS诱导的巨噬细胞氧化应激和炎症,H2S对类固醇敏感性的影响值得进一步研究。