NEW STRATEGY BASED ON REGULATION OF OXTPATIVE STRESS IN TREATMENT OF BRONCHIAL ASTHMA

基于过度应激调节的支气管哮喘治疗新策略

基本信息

批准号：
13670611
负责人：
KANAZAWA Hiroshi
金额：
$ 1.73万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

We have previously found that higher levels of nitrogen oxides in exhaled air and in induced sputum were found in asthmatics compared to normal control subjects, and that nitrogen oxides altered β_2 -adrenoceptor (β_-AR) function in an experimental animal model. Therefore, this study was designed to determine whether nitrogen oxides influence the bronchodilating activity of β_2-AR agonists in asthmatic patients. We simultaneously measured the levels of nitrogen oxides in exhaled air and in induced sputum in 20 asthmatic patients. The bronchodilating activity of β_2-AR agonists was expressed as a spontaneous recovery (pre- raethacholine) and recovery from the lowest value in FEV1 evoked by methacholine challenge (post-methacholine). For 1-week after the first study, 400 μg of beclomethasone dipropionate (BDP) twice daily was administered for all patients, and the above mentioned protocols were repeated. Recovery in FEV1 (pre-methacholine) after β_2-AR agonists was not significantly correlated with any baseline FEV1 and PC20 methacholine. Moreover, recovery in FEV1 (post-methacholine) after β_2-AR agonists was not also significantly correlated with maximal fall in FEV1 after methacholine challenge and PC20 methacholine. However, recovery in FEV1 after β_2-AR agonists was inversely correlated with NO levels in exhaled air, and concentration of nitrite and nitrate in induced sputum. After treatment with inhaled BDP for 1-week, there was no significant change in baseline FEV1. However, there was a significant decrease in the concentration of nitrite and nitrate in induced sputum. We found that change of nitrite and nitrate levels in induced sputum after 1-week BDP therapy was significantly correlated with change in bronchodilating activity of β_2-AR agonists between pre- and post-BDP therapy. We determined that nitrogen oxides in the airways reduced β_2-AR agonists-induced brochodilation in asthmatics.

我们先前已经发现，与正常对照组相比，在哮喘患者中发现了耗尽的空气和诱导的痰液中较高水平的氮氧化物，并且在实验性动物模型中，氮氧化物改变了β_2-肾上腺素受体（β_ -AR）功能。因此，该研究旨在确定氮氧化物是否影响哮喘患者中β_2-AR激动剂的支气管扩张活性。我们简单地测量了20名哮喘患者的耗尽空气和诱导的痰液中氮氧化物的水平。 β_2-ar激动剂的支气管扩张活性表示为发起的恢复（前乙酰氨基苯胺），并从Methodoline挑战（方法后）引起的FEV1中的最低值中恢复。在第一项研究后的1周中，每天两次对所有患者进行两次替代二替欧（BDP）的供应量，并重复上述方案。 β_2-AR激动剂后Fev1（甲choline前）的恢复与任何基线FEV1和PC20甲基苯胺没有显着相关。此外，β_2-ar激动剂后FEV1（甲choline后）的恢复也与FEV1和PC20甲基苯胺后FEV1的最大下降显着相关。然而，β_2-ar激动剂后Fev1的恢复与耗尽的空气中没有水平以及诱导痰液中的亚硝酸盐和硝酸盐的浓度成反比。用遗传的BDP处理1周后，基线FEV1没有显着变化。然而，在诱导的痰液中，亚硝酸盐和硝酸盐的浓度显着降低。我们发现1周BDP治疗后诱导的痰液中亚硝酸盐和硝酸盐水平的变化与BDP疗法和BDP后治疗之间的β_2AR激动剂的支气管扩张活性的变化显着相关。我们确定气道中的氮氧化物降低了β_2-ar激动剂诱导的哮喘学上的小氨基化。