M受体拮抗剂对提高慢性阻塞性肺疾病患者调节性T细胞表达的影响  

Muscarinic cholinergie receptor antagonists enhanced the expression of CD8^＋ CD25^＋ Foxp3^＋ regulary T cells in stable COPD patients

作　　者：张建初[1] 王佩[1] 熊先智[1] 邓莉[1] 辛建保[1] 马万里[1] 施焕中[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院呼吸科卫生部呼吸系疾病重点实验室,武汉430022

出　　处：《中华结核和呼吸杂志》2010年第1期33-36,共4页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：教育部博士点基金新教师项目资助（20070487154）

摘　　要：目的观察COPD稳定期患者体内是否存在CD8^＋CD25^＋Foxp3^＋调节性T细胞（Treg细胞），以及M受体拮抗剂噻托溴铵对其表达的影响。方法2007年10月至2008年3月，选择23例COPD稳定期患者，每日1次吸入噻托溴铵18μg，连续治疗3个月。分别在治疗前后检查患者的肺功能和检测外周血中T细胞亚群的数量。两组间均数比较采用配对t检验，相关分析采用直线相关分析。结果COPD稳定期患者在吸入噻托溴铵治疗后，外周血中CD4为（36±6）％，CD8^＋CD25^＋Treg细胞为（21±21）％，明显高于治疗前的（28±10）％和（8±8）％；CD4^＋CD25^＋为（4±3）％，明显低于治疗前的（10±7）％，差异均有统计学意义（t值为2．72—3．78，P〈0．01和P〈0．05）。CD8、CD8^＋CD25^＋和CD4^＋CD25^＋Treg细胞均有表达，但治疗前后无明显变化。治疗后肺通气功能得到明显改善，FEV1、FEV1占预计值％和FEV1／FVC分别由（1．0±0．3）L、（35±10）％和（41±8）％提高到（1．1±0．3）L、（40±11）％和（45±11）％，差异均有统计学意义（t值为2．37～2．65，均P〈0．05）。相关分析结果表明，治疗前后CD4^＋和CD25^＋的变化差值与CD8^＋CD25^＋Treg细胞的变化率呈显著负相关（r值分别为-0．61和-0．72，P〈0．05和P〈0．01）。结论M受体拮抗剂噻托溴铵可能具有增强细胞免疫和免疫抑制的功能。CD8^＋CD25^＋Treg和CD4^＋CD25^＋Treg可能成为了解患者免疫状况，判断疗效和疾病免疫分型的一组新指标。Objective To investigate the levels of peripheral CD8^＋ CD25^＋ Foxp3^＋ regulary T cells （CD8^＋CD25^＋Treg） in stable chronic obstructive pulmonary disease （COPD） patients, and the effect of muscarinic cholinergic receptor antagonist, tiotropium bromide, on the expression of CD8^＋ CD25^＋ Treg. Methods From Oct. 2007 to Mar. 2008, 23 patients with stable moderate to severe COPD received tiotropium bromide inhalation （ 18 μg daily） for 3 months. Before and after the use of tiotropium bromide, lung function was performed and peripheral vein blood samples were collected from the patient. Lympbocytes were isolated by three-color labeled monoclonal antibodies flow cytometry to detect the quantity and percentage of CD8^＋ T cell, CD8^＋ CD25^＋ T cell, CD^8＋ CD25^＋ Treg, CD4^＋ T cell, CD4^＋ CD25^＋ T cell and CD4^＋ CD25^＋ Treg, respectively. Paired t test was used for comparison between data before and after treatment. Results In patients with stable COPD, after tiotropiam bromide treatment, the percentage of CD4^＋ T cells was increased from （28 ± 10） % to （ 36 ±6） %, and the difference was significant （ t = 3.20, P 〈 0. 01 ）. CD4^＋CD25^＋ was decreased from （10±7）% to （4 ±3）% （t =3.78, P〈0. 01）, and CD8^＋CD25^＋Treg was increased from （8±8）% to （21 ±21）% （t=2.72, P〈0.05）. At baseline, CD8^＋ cells, CD8^＋CD25^＋ cells and CD4^＋CD25^＋ Treg were detectable in the peripheral blood, but no significant changes were observed after treatment. After treatment with tiotropium bromide, the lung function was markedly improved; FEV1, FEV1/Pre% , and FEV1/FVC were increased from （1.0 ±0. 3）L, （35 ±10）% and （41 ±8）% to （1. 1 ± 0. 3 ） L, （40± 11 ） % and （45 ± 11 ） %, respectively （ t = 2. 65, 2. 56 and 2. 37, respectively, all P 〈 0. 05 ）.By linear correlation analysis, the quantity of changes of CD4^＋ T cells and CD4^＋ CD25^＋ T cells were negatively correlated with the rate of change in CD

关 键 词：肺疾病 慢性阻塞性 T淋巴细胞 调节性 受体 毒蕈碱 

分 类 号：R563.9[医药卫生—呼吸系统]