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.

我们之前发现，与正常对照组相比，哮喘患者呼出的空气和诱导痰中的氮氧化物含量较高，并且氮氧化物改变了实验动物模型中的β_2-肾上腺素受体（β_-AR）功能。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，我们同时测量了呼出气和诱导气中的氮氧化物水平。 20 名哮喘患者的痰液中 β_2-AR 激动剂的支气管扩张活性表现为自发恢复（乙酰甲胆碱前）和首次乙酰甲胆碱激发后 1 周内从 FEV1 最低值恢复。研究中，所有患者每日两次服用 400 μg 二丙酸倍氯米松 (BDP)，上述方案为β_2-AR 激动剂后 FEV1（乙酰甲胆碱前）的恢复与任何基线 FEV1 和 PC20 乙酰甲胆碱均无显着相关性。此外，β_2-AR 激动剂后 FEV1（乙酰甲胆碱后）的恢复也与最大跌倒无关。然而，β_2-AR 激动剂后 FEV1 的恢复与 NO 呈负相关。吸入BDP治疗1周后，呼出气中亚硝酸盐和硝酸盐浓度没有显着变化，但诱导痰中亚硝酸盐和硝酸盐浓度显着降低。我们发现BDP治疗1周后诱导痰中亚硝酸盐和硝酸盐水平的变化与支气管扩张活性的变化显着相关。我们确定，BDP 治疗前和治疗后的β_2-AR 激动剂可减少哮喘患者中β_2-AR 激动剂引起的支气管扩张。