慢性阻塞性肺疾病气道中活性氮物质生成的抑制：吸入性糖皮质激素与口服茶碱的比较
Inhibition of reactive nitrogen species production in COPD airways: comparison of inhaled corticosteroid and oral theophylline.
作者信息
Hirano T, Yamagata T, Gohda M, Yamagata Y, Ichikawa T, Yanagisawa S, Ueshima K, Akamatsu K, Nakanishi M, Matsunaga K, Minakata Y, Ichinose M
机构信息
Third Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan.
出版信息
Thorax. 2006 Sep;61(9):761-6. doi: 10.1136/thx.200X.058156.
BACKGROUND
Reactive nitrogen species (RNS) are thought to be one of the important factors in the pathogenesis of chronic obstructive pulmonary disease (COPD). A study was undertaken to examine the effects of theophylline and fluticasone propionate (FP) on RNS production in subjects with COPD.
METHODS
Sixteen COPD subjects participated in the study. Theophylline (400 mg/day orally) or FP (400 mug/day inhalation) were administered for 4 weeks in a randomised crossover manner with a washout period of 4 weeks. Induced sputum was collected at the beginning and end of each treatment period. 3-nitrotyrosine (3-NT), which is a footprint of RNS, was quantified by high performance liquid chromatography with an electrochemical detection method as well as by immunohistochemical staining.
RESULTS
Theophylline significantly reduced the level of 3-NT in the sputum supernatant as well as the number of 3-NT positive cells (both p<0.01). FP also reduced 3-NT formation, but the effect was smaller than that of theophylline. Theophylline also significantly reduced the neutrophil cell counts in the sputum (p<0.01), while FP treatment had no effect on the number of inflammatory cells in the sputum, except eosinophils.
CONCLUSIONS
Theophylline reduces nitrative stress and neutrophil infiltration in COPD airways to a larger extent than inhaled corticosteroid.
背景
活性氮物质（RNS）被认为是慢性阻塞性肺疾病（COPD）发病机制中的重要因素之一。本研究旨在探讨茶碱和丙酸氟替卡松（FP）对COPD患者RNS产生的影响。
方法
16名COPD患者参与了本研究。茶碱（口服400mg/天）或FP（吸入400μg/天）以随机交叉方式给药4周，洗脱期为4周。在每个治疗期开始和结束时收集诱导痰。采用高效液相色谱电化学检测法和免疫组化染色法对作为RNS印记的3-硝基酪氨酸（3-NT）进行定量分析。
结果
茶碱显著降低了痰上清液中3-NT的水平以及3-NT阳性细胞的数量（均p<0.01）。FP也减少了3-NT的形成，但效果小于茶碱。茶碱还显著降低了痰中的中性粒细胞计数（p<0.01），而FP治疗对痰中炎症细胞数量无影响，但对嗜酸性粒细胞有影响。
结论
茶碱比吸入性糖皮质激素能更大程度地减轻COPD气道中的硝化应激和中性粒细胞浸润。
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