COPD患者外周血单核细胞中HDAC活性及其及肺功能及吸烟关系.doc

COPD患者外周血单核细胞中HDAC活性及其及肺功能及吸烟关系[摘要] 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/(Lμg)和(21.39±4.92) μmol/(Lμg),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/(Lμg)和(21.39±4.92) μmol/(Lμg),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。 [关键词] 组蛋白去乙酰化酶;吸烟;慢性阻塞性肺病 [中图分类号] R563[文献标识码]A [文章编号]1673-7210(2009)07(c)-016-04 Relationship between HDAC activity and lung function as well as smoking in peripheral blood mononuclear cells of COPD patients CHEN Yanwei1, YANG Jiong2 (1.Department of Pulmonary Medicine, Shenzhen Nanshan Hospital of Guangdong Medical College, Shenzhen518052, China; 2.Department of Pulmonary Medicine, People’s Hospital of Wuhan University, Wuhan 430060, China) [Abstract] 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 assmoking 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 sig