六补气血胶囊对稳定期慢性阻塞性肺疾病合并肺气虚患者CD4CD25Foxp3调节性T细胞、辅助性T细胞及肺功能的影响
Effect of Liuweibuqi capsules on CD4CD25Foxp3 regulatory T cells, helper T cells and lung function in patients with stable chronic obstructive pulmonary disease complicated with lung Qi deficiency.
作者信息
Wang Cheng-Yang, Ding Huan-Zhang, Tang Xiao, Li Ze-Geng
机构信息
Department of Traditional Chinese Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Graduate School of Anhui University of Chinese Medicine, Hefei 230038, China.
出版信息
J Thorac Dis. 2018 May;10(5):2700-2711. doi: 10.21037/jtd.2018.04.110.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is predicted to become the fifth leading cause of disability and the third leading cause of death around the world by 2020. Though it is potentially treatable and preventable, evidence of brain structural alterations in COPD remains sparse and conflicting. We aim to investigate the effect of Liuweibuqi capsules on CD4CD25 Forkhead box protein 3 (Foxp3) regulatory T cells (Tregs), helper T cells (Th) and lung function in patients with stable COPD complicated with lung Qi deficiency.
METHODS
COPD patients with lung Qi deficiency [458] were assigned into non-smoking COPD (NS-COPD), non-smoking control (NS-control), smoking COPD (S-COPD) and smoking control (S-control) groups, and healthy volunteers [245] into the non-smoking healthy (NSH) and smoking healthy (SH) groups. Levels of inflammatory cytokines were detected by Enzyme-linked immunoassay (ELISA). Contents of inflammatory cells, inflammatory marker, and CD4CD25Fox3Tregs were measured by flow cytometry. FEV1/FVC (%) and FEV1 (%) were detected by pulmonary function test apparatus. Correlation between FEV1 (%) and Th1, Th2, Th17, Th1/Th2 or CD4CD25Fox3Tregs was analyzed by Spearman rank correlation test. The related factors affecting treatment efficacy was assessed by logistic analysis.
RESULTS
COPD patients and smoking people showed higher level of INF-γ, IL-4, IL-17, Th1, Th2, Th17 and Th1/Th2 but lower level of CD4CD25Fox3Tregs. Liuweibuqi capsules could decrease level of inflammatory cells, cytokines, and markers (especially Th17 and IL-17), and increase level of CD4CD25Fox3Tregs. FEV1 (%) negatively correlated with Th1, Th2, Th17 and Th1/Th2 but positively correlated with CD4CD25Fox3Tregs, and smoking may strengthen their correlation, but Liuweibuqi capsules may weaker their correlation. Levels of inflammatory cytokines, cells, marker, CD4CD25Fox3Tregs, FEV1/FVC (%), FEV1 (%), smoking and Liuweibuqi capsules are factors affecting efficacy.
CONCLUSIONS
Taken together, our data support the notion that smoking is an important factor to induce and aggravate COPD. Liuweibuqi capsules could stimulate proliferation of CD4CD25Fox3Tregs and decrease Th17 expression to improve the lung function in stable COPD patients with lung Qi deficiency, and it had obvious efficacy for smoking COPD patients.
背景
预计到2020年，慢性阻塞性肺疾病（COPD）将成为全球第五大致残原因和第三大死亡原因。尽管COPD具有潜在的可治疗性和可预防性，但关于COPD脑结构改变的证据仍然稀少且相互矛盾。我们旨在研究六君子胶囊对稳定期COPD合并肺气虚患者的CD4⁺CD25⁺叉头框蛋白3（Foxp3）调节性T细胞（Tregs）、辅助性T细胞（Th）及肺功能的影响。
方法
将458例肺气虚的COPD患者分为非吸烟COPD（NS-COPD）组、非吸烟对照组（NS-control）、吸烟COPD（S-COPD）组和吸烟对照组（S-control），将245例健康志愿者分为非吸烟健康组（NSH）和吸烟健康组（SH）。采用酶联免疫吸附测定（ELISA）法检测炎症细胞因子水平。采用流式细胞术检测炎症细胞、炎症标志物及CD4⁺CD25⁺Foxp3⁺Tregs的含量。采用肺功能测试仪检测第1秒用力呼气容积/用力肺活量（FEV1/FVC）（%）和第1秒用力呼气容积（FEV1）（%）。采用Spearman等级相关检验分析FEV1（%）与Th1、Th2、Th17、Th1/Th2或CD4⁺CD25⁺Foxp3⁺Tregs的相关性。采用logistic分析评估影响治疗效果的相关因素。
结果
COPD患者及吸烟者的干扰素-γ（INF-γ）、白细胞介素-4（IL-4）、白细胞介素-17（IL-17）、Th1、Th2、Th17及Th1/Th2水平较高，而CD4⁺CD25⁺Foxp3⁺Tregs水平较低。六君子胶囊可降低炎症细胞、细胞因子及标志物（尤其是Th17和IL-17）水平，并提高CD4⁺CD25⁺Foxp3⁺Tregs水平。FEV1（%）与Th1、Th2、Th17及Th1/Th2呈负相关，与CD4⁺CD25⁺Foxp3⁺Tregs呈正相关，吸烟可能增强它们之间的相关性，但六君子胶囊可能减弱它们之间的相关性。炎症细胞因子、细胞、标志物、CD4⁺CD25⁺Foxp3⁺Tregs、FEV1/FVC（%）、FEV1（%）、吸烟及六君子胶囊是影响疗效的因素。
结论
综上所述，我们的数据支持吸烟是诱导和加重COPD的重要因素这一观点。六君子胶囊可刺激CD4⁺CD25⁺Foxp3⁺Tregs增殖并降低Th17表达，从而改善稳定期COPD合并肺气虚患者的肺功能，且对吸烟的COPD患者有明显疗效。
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