慢性阻塞性肺疾病患者和吸烟肺功能正常者体内HIF-1α表达及意义

Expression and significance of hypoxia-inducible factor-1α in patients with chronic obstructive pulmonary disease and smokers with normal lung function

目的探讨低氧诱导因子-1α(HIF-1α)在慢性阻塞性肺疾病(COPD)患者和吸烟肺功能正常者肺组织和血清中表达及其临床意义。方法肺组织标本取自手术治疗的周围型肺癌患者,共32例,检测术前肺功能,将其分为吸烟COPD稳定期组(COPD组,n=10),吸烟肺功能正常组(n=12),不吸烟肺功能正常组(n=10)。术前清晨空腹取血清,术后取癌旁肺组织,ELISA检测血清和肺组织匀浆HIF-1α含量,免疫组织化学方法检测肺组织HIF-1α的表达,并分析HIF-1α表达水平与肺功能指标的相关关系。结果 COPD稳定期组、吸烟肺功能正常组、不吸烟肺功能正常组患者血清HIF-1α含量分别为(73.25±6.12)pg/mL、(60.30±8.00)pg/mL、(47.03±8.43)pg/mL;吸烟肺功能正常组和COPD组明显高于不吸烟肺功能正常组(P<0.01),COPD组明显高于吸烟肺功能正常组(P<0.01)。COPD稳定期组、吸烟肺功能正常组、不吸烟肺功能正常组患者肺组织匀浆HIF-1α含量分别为(2.04±0.24)pg/μg、(1.67±0.34)pg/μg、(1.12±0.33)pg/μg;吸烟肺功能正常组和COPD组明显高于不吸烟肺功能正常组(P<0.01),COPD组明显高于吸烟肺功能正常组(P<0.01)。HIF-1α广泛表达于COPD组肺泡和气道上皮细胞、肺小动脉壁的炎症细胞以及巨噬细胞中。血清和肺组织匀浆中HIF-1α含量均与第1秒用力呼气容积与用力肺活量比(FEV1/FVC)、第1秒钟用力呼气容积占预计值百分比(FEV1%pred)呈显著负相关。结论 COPD患者和吸烟肺功能正常者肺组织和血清HIF-1α的表达增加,与气流受限有关。

Objective To study the expression of hypoxia-inducible factor （ HIF）-1α in lung tissues and sera from chronic obstructive pulmonary disease （COPD） patients and smokers with normal lung function and explore its clinical significance. Methods Lung tissue samples were obtained from 32 patients undergoing surgery for peripheral lung tumors. Lung function test was performed before lung cancer surgery, Based on lung function and smoking status, 32 patients were devided into three groups： smokers with stable COPD （COPD group, n = 10）, smokers with normal lung function （S group, n = 10） and nonsmokers with nomal lung function （NS group, n = 10）. The preoperative fasting sera and lung tissues as far as possible away from the tumor site from all patients were collected： HIF-1α levels in sera and lung tissue homogenates were evaluated by ELISA. The expression of HIF-1α in airway epithelium, alveolar wall and blood vessel wall were detected by immunohistocherristry. Furthermore, the correlation between HIF-1α expression levels and pulmonary function was analyzed. Results Serum HIF-1α levels were significantly elevated in COPD group [（73.25 ±6.12） pg/mL] and S group [（60.30 ±8.00） pg/mL] as compared with NS group [ （47.03 ± 8.43 ） pg/mL, P 〈 0.01 ], and COPD group was significantly higher than S group （P 〈0.01 ）. The concentrations of HIF-1α in lung tissue homogenates significantly increased in COPD group [ （2.04 ± 0.24） pg/μg] and S group [（1.67 ±0.34） pg/μg] as compared with NS group [（1. 12 ±0.33） pg/μg, P〈0. 01], and COPD group was also significantly higher than S group （P 〈 0.01）. HIF-1α expression was located in inflammatory cells and macrophages of airway epithelium, alveolar wall and small pulmonary artery wall, HIF-1α levels in sera and lung tissue homogenates showed negative correlations with FEV1/FVC and FEV1% predicted. Conclusion HIF-1α levels are raised in sera and lung tissues of COPD patients and smokers with normal lung function, and they were positively correlated with the severity of airflow limitation.