核因子κB和缺氧诱导因子1在慢性阻塞性肺疾病患者外周血单个核细胞中的表达  

Expression of NF-κB and HIF-1 in PBMC of patients with chronic obstructive pulmonary disease

作　　者：罗玲[1] 高兴林[2] 李东风[2] 吴健[2] 林琦[2] 罗少华[2] 

机构地区：[1]南方医科大学,广州510515 [2]广东省人民医院东病区呼吸科广东省医学科学院广东省老年医学研究所,广州510080

出　　处：《国际呼吸杂志》2012年第3期188-192,共5页International Journal of Respiration

基　　金：广东省科技计划（2009B030801260）;广东省医学科研基金（B2009001）

摘　　要：目的探讨核因子κB（NF-κB）和缺氧诱导因子1（HIF-1）在老年慢性阻塞性肺疾病（COPD）患者外周血单个核细胞（PBMC）中的表达，明确NF-κB和HIF-1在COPD发病机制中的作用。方法通过Western blotting法、实时荧光定量PCR法分别测定稳定期COPD患者（中度以上，30例）、对照组（30例）PBMC的NF—κB、HIF-1蛋白水平和NF-κB、HIF-1mRNA水平。结果COPD组PBMC细胞中NF-κBmRNA、HIF-1mRNA水平均显著高于对照组（0．013±0．010比0．005±0．003，P〈0．01；0．030±0．025比0．008±0．006，P〈0．01）。COPD组PBMC细胞核中NF-κB、HIF-1蛋白表达均高于对照组，差异有统计学意义（1．08±0．12比0．87±0．09，P〈0．01；1．12±0．09比0．97±0．17，P=0．002）。NF—κB蛋白在各COPD组差异有统计学意义（P〈0．01），与FEV1％pred呈显著负相关（r=-0．657，P〈0．01）。NF-κBmRNA、HIF-1mRNA、HIF-1蛋白在各COPD组差异均无统计学意义，与FEV1％pred均无相关性（P值均〉0．05）。NF—κBmRNA与HIF-1mRNA呈正相关（r=0．673，P〈0．01），NF—κB、HIF-1蛋白表达呈正相关（r=0．56，P=0．001）。结论COPD患者PBMC中NF—κB、HIF-1mRNA水平及蛋白水平表达均增加，且HIF-1在各严重程度的COPD中稳定表达，NF—κB蛋白表达与疾病严重程度相关。表明中度以上COPD患者在慢性持续性缺氧的情况下既启动了全身的炎症反应同时也启动了适应性保护机制。Objective To investigate the expression of NF-κB and HIF-1 in elderly patients with chronic obstructive pulmonary disease （COPD）, and the role of them in the pathogenesis of COPD. Methods Western blotting and real-time quantitative PCR methods were measured in peripheral blood mononuclear cells （PBMC） of patients with stable COPD group （moderate and over, 30 cases） and the matched control group （ n = 30） to detect the expression the levels of NF-κB, HIF-1 protein and NF-κB, HIF-1 mRNA. Results NF-κB mRNA, HIF-1 mRNA levels in PBMC were significantly higher in COPD group than in control group （0.013±0.010 vs 0.005±0.003, P 〈0.01,0.030±0.025 vs 0.008±0. 006, P 〈0.01）. Nuclei NF-κB, HIF-1 protein expression were significantly higher in COPD group than in control group （1.08±0.12 vs 0. 87±0. 09, P 〈0.01,1.12±0.09 vs 0. 97±0.17, P =0. 002）. There were differences of NF-κB protein in the different stages COPD （ P 〈0.01）, and FEV1 pred was significantly negatively correlated with NF-κB （r =-0. 657, P 〈0.01）. There were no significant differences of NF-κB mRNA, HIF-1 mRNA and HIF-1 protein in the different stages COPD, no correlations with FEV1 %pred, （ P 〉0.05）. There were positive correlations between NF-κB mRNA and HIF-lmRNA （r =0.673, P 〈0.01）, between NF-κB protein and HIF-1 protein （r =0.56, P =0. 001）. Conclusions Expression of NF-κB, HIF-1 mRNA and protein in PBMC of patients with COPD were increased. HIF-1 stable expresses throughout the different severity of COPD. The expression of NF-κB protein has correlation of disease severity. It shows that under chronic persistent hypoxia the systemic inflammatory response and the adaptive protection mechanisms are activated in moderate to very severe COPD patients.

关 键 词：缺氧诱导因子1 核因子ΚB 肺疾病 慢性阻塞性肺疾病 

分 类 号：R563.9[医药卫生—呼吸系统]