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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670611/
• 关键词: NITRIC OXIDE; AIRWAY HYPERREACTIVITY; β_2-ADRENQCEPTOR AGONIST; AIRWAY INFLAMMATION; 気管支喘息; 運動誘発喘息; 血管新生; 血管透過性; 窒素酸化物; 気道内窒素酸化物; 抗酸化能

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.

我们曾在实验动物模型中发现哮喘患者呼出气和诱导痰中的氮氧化物含量高于正常对照组，并且氮氧化物改变了β_2 -肾上腺素能受体（β_2-AR）的功能。因此，本研究旨在探讨氮氧化物是否影响β_2-AR激动剂对哮喘患者的支气管扩张活性。同时测定了20例哮喘患者呼出气和诱导痰中氮氧化物的含量。β_2-AR激动剂的支气管扩张活性表现为乙酰甲胆碱激发前FEV_1的自发恢复和乙酰甲胆碱激发后FEV_1从最低值恢复。首次研究后1周，所有患者均给予二丙酸倍氯米松（BDP）400 μg，每日2次，并重复上述方案。β_2-AR激动剂治疗后FEV 1（前乙酰甲胆碱）的恢复与任何基线FEV 1和PC 20乙酰甲胆碱均无显著相关性。此外，β_2-AR激动剂后FEV 1（乙酰甲胆碱后）的恢复与乙酰甲胆碱激发和PC 20乙酰甲胆碱后FEV 1的最大下降也无显著相关性。β_2-AR激动剂治疗后FEV_1的恢复与呼出气中NO、诱导痰中NO_2 ~-、NO_3 ~-浓度呈负相关。吸入BDP治疗1周后，基线FEV 1无显著变化。但诱导痰中亚硝酸盐和硝酸盐浓度明显降低。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BDP治疗前后β_2-AR激动剂支气管扩张活性的变化显著相关。我们确定气道中的氮氧化物减少了哮喘患者β_2-AR激动剂诱导的支气管扩张。

项目成果

Hiroshi Kanazawa et al.: "Nitrogen oxides reduce albuterol-induced bronchodilation in patients with b ronchial asthma"Respiration. (In press).

Hiroshi Kanazawa 等人：“氮氧化物可减少支气管哮喘患者沙丁胺醇诱导的支气管扩张”呼吸。

Kanazawa H, et al.: "Nitrogen oxides reduce albuterol-induced bronchodilator in patients with bronchial asthma"Respiration. 69. 490-495 (2002)

Kanazawa H 等人：“氮氧化物可减少支气管哮喘患者沙丁胺醇诱导的支气管扩张剂”呼吸。

Kanazawa H, et al.: "Vascular involvement in exercise-induced airway narrowing in patients with bronchial asthma"chest. 122. 166-170 (2002)

Kanazawa H 等人：“支气管哮喘患者运动引起的气道狭窄中的血管受累”胸部。

Kanazawa H, et al.: "Decreased peroxynitrite inhibitory activity in induced sputum in patients with bronchial asthma"Thorax. 57. 509-512 (2002)

Kanazawa H 等人：“支气管哮喘患者诱导痰液中过氧亚硝酸盐抑制活性降低”Thorax。

Kanazawa H, Asai K, Hirata K, Yoshikawa J: "Vascular involvement in exercise-induced airway narrowing in patients with bronchial asthma"Chest. 122. 166-170 (2002)

Kanazawa H、Asai K、Hirata K、Yoshikawa J：“支气管哮喘患者运动引起的气道狭窄中的血管受累”胸部。