六味补气胶囊对慢性阻塞性肺疾病患者CD4＋CD25＋Foxp3＋调节性T细胞、辅助性T细胞的影响

Effects of Liuwei Buqi capsules on CD4＋CD25＋forkhead box protein 3＋regulatory T cells,helper T cells in patients with chronic obstructive pulmonary disease

目的：观察六味补气胶囊对慢性阻塞性肺疾病（COPD）患者CD4＋CD25＋Foxp3＋调节性T细胞（Treg）、辅助性T细胞（Th）的影响。方法选择2012年1月至2013年5月安徽中医药大学第一附属医院收住的COPD患者80例，按随机原则分为中药试验组和西药对照组，每组40例；另选取本院科研志愿者40例为健康对照组。中药试验组和西药对照组患者入院后均给予常规西医综合治疗，中药试验组在常规治疗基础上加服六味补气胶囊，每次3粒（0.4 g/粒），每日2次；西药对照组在常规治疗基础上加服硝苯地平，每次10 mg，每日3次，两组均30 d为1个疗程。对两组COPD患者治疗前后进行BODE〔体质量指数（B）、气流阻塞程度（O）、呼吸困难（D）及运动能力（E）〕评分、呼吸困难评分；采用肺功能仪观察患者肺功能变化；采用酶联免疫吸附试验（ELISA）检测血清γ-干扰素（IFN-γ）、白细胞介素（IL-4、IL-17）、Th1/Th2的变化；采用流式细胞术检测外周血Treg的表达。结果与健康对照组比较，COPD组患者肺功能参数、IL-4、CD4＋CD25＋Treg、CD4＋CD25＋Foxp3＋Treg均升高，呼吸困难评分、BODE评分、IFN-γ、Th1/Th2、IL-17均明显降低（P＜0.05或P＜0.01）；与本组治疗前比较，两组治疗后肺功能参数第1秒用力呼气容积（FEV1）、FEV1占用力肺活量的百分比（FEV1/FVC）、IL-4、CD4＋CD25＋Treg、CD4＋CD25＋Foxp3＋Treg均升高，呼吸困难评分、BODE评分、IFN-γ、Th1/Th2、IL-17均降低（P＜0.05或P＜0.01）。西药对照组治疗后最大呼气流量（PEF）降低，中药试验组升高。中药试验组和西药对照组治疗后FEV1/FVC〔（78.12±14.96）%比（67.52±10.39）%〕、BODE评分（分：1.07±0.72比1.77±0.74）、IL-17（μg/L：40.80±8.97比48.22±6.51）、Th1/Th2（1.05±0.23比1.42±0.21）、CD4＋CD25＋Foxp3＋Treg〔（6.61±2.26）%比（5.25±2.03）%〕比较差异均有统计学意义（均P＜0.05）。结论六味补气胶囊通过上调COPD患者CD4＋CD25＋Foxp3＋Treg、IL-4表达，下调IFN-γ、IL-17表达，纠正Th1/Th2平衡，改善COPD症状。

Objective To observe the effects of Liuwei Buqi capsules on CD4＋CD25＋forkhead box protein 3＋（Foxp3＋）regulatory T cells（Tregs）,helper T cells（Ths）in patients with chronic obstructive pulmonary disease （COPD）. Methods Eighty COPD patients admitted into the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from January 2012 to May 2013 were randomly divided into a traditional Chinese medicine （TCM）experimental group（40 cases）and a western medicine control group（40 cases）;there were 40 research volunteers enrolled as healthy controls. After admission,both the TCM experimental group and western medicine control group were given conventional western medicine comprehensive treatment. Additionally,in the TCM experimental group,Liuwei Buqi capsules were given orally once 3 pills（0.4 g/pill）and twice a day,while in the western medicine control group nifedipine was given,once 10 mg and 3 times a day,30 days constituting one therapeutic course for both groups. BODE evaluation means that the body mass index（B）,the degree of airflow obstruction（O）,the scores of dyspnea（D）and excercise capacity（E）of COPD patients were evaluated. A spirometer was used to observe the changes in the patient＇s pulmonary function to detect the dyspnea score. The γ-interferon（IFN-γ）,interleukin （IL-4 and IL-17）in serum were detected by enzyme-linked immunosorbent assay（ELISA）. The expression of Treg of peripheral blood was detected by flow cytometry. Results Compared with healthy control group,lung function parameters,IL-4,CD4＋CD25＋Treg and CD4＋CD25＋Foxp3＋Treg of peripheral blood were increased,while dyspnea score,BODE score,the expressions of IFN-γ,Th1/Th2,IL-17 in serum were decreased significantly in the COPD group（P〈0.05 or P〈0.01）. After treatment,compared with those before treatment in the two groups, the forced expiratory volume in 1 second（FEV1）,FEV1/forced vital capacity（FVC）,IL-4,CD4＋CD25＋Treg, CD4＋CD25＋Foxp3＋ Treg were all increased,while dyspnea score,BODE score,IFN-γ,Th1/Th2,IL-17 were all decreased（P〈0.05 or P〈0.01）,and the peak expiratory flow（PEF）was decreased in western medicine control group and increased in TCM experimental group. After treatment,the comparisons of ratio of FEV1/FVC〔（78.12±14.96）%vs.（67.52±10.39）%〕,BODE score（1.07±0.72 vs. 1.77±0.74）,IL-17（μg/L：40.80±8.97 vs. 48.22±6.51） Th1/Th2（1.05±0.23 vs. 1.42±0.21）and CD4＋CD25＋Foxp3＋ Treg〔（6.61±2.26）% vs.（5.25±2.03）%〕between the two groups were all of statistical significant difference（all P〈0.05）. Conclusion Liuwei Buqi capsules can improve COPD symptoms by up-regulating the expressions of CD4＋CD25＋Foxp3＋ Treg,IL-4,and down-regulating the expressions of IFN-γ,IL-17 to correct the balance of Th1/Th2 in patients with COPD.