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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
引用本文:张建初,王佩,熊先智,邓莉,辛建保,马万里,施焕中.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[J].中华结核和呼吸杂志,2010,33(1).
作者姓名:张建初  王佩  熊先智  邓莉  辛建保  马万里  施焕中
作者单位: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
基金项目:教育部博士点基金新教师项目 
摘    要:目的 观察COPD稳定期患者体内是否存在CD_8~+CD_(25)~+Foxp_3~+调节性T细胞(Treg细胞),以及M受体拈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18 μg,连续治疗3个月.分别在治疗前后榆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,外周血巾CD_4~+为(36±46)%,CD_8~+CD_(25)~+Treg 细胞为(21±21)%,明显高于治疗前的(28±10)%和(8±8)%;CD_4~+CD_(25)~+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).CD_8~+、CD_8~+CD_(25)~+和CD_4~+CD_(25)~+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,FEV_1、FEV_1占预计值%和FEV_1/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
关 键 词:肺疾病  慢性阻塞性  T淋巴细胞  调节性  受体  毒蕈碱

Muscarinic cholinergic receptor antagonists enhanced the expression of CD_8~+CD_(25)~+Foxp_3~+ regulary T cells in stable COPD patients
ZHANG Jian-chu,WANG Pei,XIONG Xian-zhi,DENG Li,XIN Jian-bao,MA Wan-li,SHI Huan-zhong.Muscarinic cholinergic receptor antagonists enhanced the expression of CD_8~+CD_(25)~+Foxp_3~+ regulary T cells in stable COPD patients[J].Chinese Journal of Tuberculosis and Respiratory Diseases,2010,33(1).
Authors:ZHANG Jian-chu  WANG Pei  XIONG Xian-zhi  DENG Li  XIN Jian-bao  MA Wan-li  SHI Huan-zhong
Abstract:Objective To investigate the levels of peripheral CD_8~+CD_(25)~+Foxp_3~+ regnlary T cells (CD_8~+CD_(25)~+ Treg)in stable chronic obstructive pulmonary disease(COPD)patients,and the effect of muscarinic cholinergic receptor antagonist,tiotropium bromide,on the expression of CD_8~+ CD_(25)~+ Treg.Methods From Oct.2007 to Mar.2008,23 patients with stable moderate to severe COPD received tiotropium bromide inhalation(1 8 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.Lymphocytes were isolated by three-color labeled monoelonal antibodies flow cytometry to detect the quantity and percentage of CD_8~+ T cell,CD_8~+ CD_(25)~+ T cell,CD_8~+ CD_(25)~+ Treg,CD_4~+ T cell,CD_4~+ CD_(25)~+ T cell and CD_4~+ CD_(25)~+ Treg,respectively.Paired t test was used for comparison between data before and after treatment.Results In patients with stable COPD.after tiotropium bromide treatment,the percentage of CD_4~+ T cells was increased from(28±10)% to (36±6)%,and the difference was significant(t=3.20,P<0.01).CD_4~+CD_(25)~+ was decreased from(10±7)%to(4±3)%(t=3.78,P<0.01),and CD_8~+ CO_(25)~+ Treg was incteased from(8±8)%to(21±21)%(t=2.72,P<0.05).At baseline,CD_8~+ cells,CD_8~+ CD_(25)~+ cells and CD_~+ CD_(25)~+ Treg were detectable in the peripheral blood,but no significant changes were observed after trealmenL After ireatment with tiotropium bromide,the lung function was markedly improved;FEV_1,FEV_1/Pre%.and FEV_1/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 CD_4~+ T cels and CD_4~+ cD_(25)~+ T cells were negatively correlated with the rate of change in CD_8~+ CD_(25)~+ Treg(r=-0.61,P<0.05 and r=-0.72,P<0.01,respectively).Conclusions In the peripheral blood of patients with stable COPD.there was expression of CD_8~+ CD_(25)~+ Treg and CD_4~+ CD_(25)~+ Treg The muscarinic receptor antagonist tiotropium bromide,promoted the amplification of CD_4~+,inhibited the expression of CD_(25)~+,and enhanced the expression of CD_8~+ Treg,suggesting that muscarinic receptor antagonist tiotropium bromide may possess immunomodulation function.
Keywords:Pulmonary disease  chronic obstructive  T-lymphocytes  regulatory  Receptors  muscarinic
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