COPD患者外周血单核细胞中HDAC活性及其与肺功能和吸烟的关系

Relationship between HDAC activity and lung function as well as smoking in peripheral blood mononuclear cells of COPD patients

目的:观察慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)患者外周血单核细胞(peripheral blood mononuclear cells,PBMC)组蛋白去乙酰化酶(histone deacetylase,HDAC)的活性及其与气流受限和吸烟量的关系。方法:募集COPD患者及吸烟和非吸烟健康志愿者并检测其肺功能。抽取所有被研究者外周静脉血,以密度梯度离心法分离出外周血单核细胞。提取组蛋白并测定HDAC活性。记录所有被研究者的肺功能及吸烟情况。结果:COPD患者外周血单核细胞总HDAC活性比健康非吸烟者低40%[(12.86±6.14)μmol/(L·μg)和(21.39±4.92)μmol/(L·μg),P=0.000],在1、2、3期均有显著性差异;健康吸烟者外周血单核细胞总HDAC活性较健康非吸烟者低40%[(12.50±4.27)μmol/(L·μg)和(21.39±4.92)μmol/(L·μg),P=0.000]。外周血单核细胞HDAC活性与吸烟量(包年)呈负相关(在COPD患者中,r=-0.867,P=0.000;在所有被研究者中,r=-0.607,P=0.000)。吸烟量达到35包年后的COPD患者外周血单核细胞HDAC活性平均值较吸烟量低于35包年者降低一半以上。结论:吸烟是造成COPD患者外周血单核细胞中HDAC活性下降的重要原因之一。COPD外周血单核细胞HDAC活性与肺通气功能(FEV1、FEV1%、FVC、FVC%和FEV1/FVC)零相关,提示吸烟对肺部的局部损害与全身损害可能有着不同的机制。

Objective： To investigate the histone deacetylase （HDAC） activity in peripheral blood mononuclear cells （PBMC） of COPD patients, and determine the relationship between HDAC activity in PBMC and lung function as well as smoking quantity in COPD patients. Methods： COPD patients, healthy smokers and healthy nonsmokers were selected in our study. The peripheral blood of all subjects were obtained, and PBMC was separated via density gradient centrifugation. Histone was extracted and HDAC activity was detected. The lung function, smoking information of all subjects were recorded. Results： HDAC activity in PBMC from COPD patients was decreased by 40% compared with normal nonsmokers [（12.86±6.14）μmol/（L.μg） and （21.39±4.92） μmol/（L.μg）, P=0.000）], this decrease showed statistical significance in stage 1, 2 and 3. HDAC activity in PBMC from healthy smoker was 40% lower than healthy nonsmokers [（12.50±4.27） μmol/（L.μg） and （21.39±4.92） μmol/（L .μg）, P=0.000]. HDAC activity in PBMC from COPD was negatively correlated with smoking quantity （r=-0.867, P=-0.000 for COPD patients; r=-0.607, P=0.000 for all subjects）. In COPD patients who smoked more than 35 pack years and smoked less than 35 pack years, the HDAC activity in PBMC of the former decreased more than a half than that of the later. Conclusion： Smoking is one of the important reasons causing the decrease of HDAC activity in PBMC of COPD patients. HDAC activity in PBMC of COPD patients shows zero correlation with lung function （FEV, FEV1%, FVC, FVC% and FEV1/FVC）, suggesting smoking may have different mechanisms on the local and whole damage of lung.