Pulmonary and Critical Care Medicine Division and Victoria Johnson Center for Obstructive Lung Diseases, Virginia Commonwealth University, Richmond, VA, USA.
Eur Respir J. 2011 Apr;37(4):775-83. doi: 10.1183/09031936.00022910. Epub 2010 Jun 18.
The pathobiology of chronic obstructive pulmonary disease (COPD) is not completely understood. The aim of this study was to assess the expression of hypoxia inducible factor (HIF)-1α in lung tissue from patients with COPD/emphysema. Lung tissue samples from 26 patients were included in this study. Seven samples were obtained from patients with normal lung function, the remainder of the samples were taken from patients with moderate COPD (n = 6; stage I and II Global Initiative for Chronic Obstructive Lung Disease classification) and severe COPD (n = 13; stage III and IV). We analysed mRNA and protein expression in the lung tissue samples and found that: 1) HIF-1α and histone deacetylase 2 proteins were significantly decreased and were correlated; 2) HIF-1α and vascular endothelial growth factor (VEGF) proteins, and forced expiratory volume in 1 s % predicted were correlated in all patients; 3) the changes in VEGF and HIF-1α protein levels in all patients were not age-related and not related to the pack-yr smoking history; and 4) the reduced HIF-1α protein expression was seen in lung endothelial cells and alveolar septal cells by immunohistochemistry. In conclusion, reduced expression of HIF-1α protein in severe COPD is consistent with the concept of a lung structure maintenance programme which is impaired on a molecular level.
慢性阻塞性肺疾病（COPD）的发病机制尚不完全清楚。本研究旨在评估缺氧诱导因子（HIF）-1α在COPD/肺气肿患者肺组织中的表达。本研究纳入了 26 例患者的肺组织样本。其中，7 例取自肺功能正常的患者，其余样本取自中度 COPD（n=6；GOLD 分级 I 和 II 期）和重度 COPD（n=13；GOLD 分级 III 和 IV 期）患者。我们分析了肺组织样本中的 mRNA 和蛋白表达，发现：1）HIF-1α和组蛋白去乙酰化酶 2 蛋白显著减少且呈正相关；2）在所有患者中，HIF-1α和血管内皮生长因子（VEGF）蛋白与用力呼气量占预计值百分比呈正相关；3）在所有患者中，VEGF 和 HIF-1α蛋白水平的变化与年龄无关，也与吸烟包年史无关；4）免疫组化显示，重度 COPD 患者的肺内皮细胞和肺泡间隔细胞中 HIF-1α 蛋白表达减少。综上所述，重度 COPD 患者 HIF-1α 蛋白表达减少与肺结构维持计划受损的概念一致，这种受损是在分子水平上发生的。
