Oral N-acetylcysteine attenuates the rat pulmonary inflammatory response to antigen
Oral N-acetylcysteine attenuates the rat pulmonary inflammatory response to antigen
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DOI：
10.1183/09031936.03.00039602
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发表时间：
2003-03-01
影响因子：
24.3
通讯作者：
Morcillo, EJ
中科院分区：
文献类型：
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作者：
Blesa, S;Cortijo, J;Morcillo, EJ
氧化应激参与了包括哮喘在内的炎症性气道疾病的病理生理过程，因此，抗氧化剂可能在哮喘治疗中具有临床益处。在攻击前，每天给予N-乙酰半胱氨酸（口服给予3mmol.kg（-1）），持续1周，并研究各种抗原诱导的肺反应。抗原暴露增加了支气管肺泡灌洗液（BALF）中的脂质过氧化和肺组织中的氧化型谷胱甘肽水平2小时后的挑战。肺核转录因子-kappaB-结合活性增加2小时后的挑战，BALF肿瘤坏死因子-α和诱导型一氧化氮合酶在肺表达达到高峰后4小时的挑战。细胞间粘附分子1和粘蛋白MUC 5AC的表达也在攻击后4小时增加。这些变化的氧化状态，转录因子活化，炎症细胞因子和基因表达的N-乙酰半胱氨酸减少。这种硫醇不影响麻醉大鼠对抗原的立即支气管痉挛反应，但抑制气道对5-羟色胺的高反应性和BALF中嗜酸性粒细胞数量的增加，这在清醒大鼠暴露于抗原气雾剂后24小时出现，这些结果表明，口服N-甲基-N，N-二甲基-N，N乙酰半胱氨酸在实验性哮喘中发挥抗氧化保护作用并减轻肺部炎症。
Oxidative stress is involved in the pathophysiology of inflammatory airway diseases including asthma; therefore, antioxidants might be of clinical benefit in asthma treatment. In the present study, the effects of N-acetylcysteine on sensitised brown Norway rats were examined.N-Acetylcysteine (3 mmol.kg body weight(-1) administered orally) was given daily for 1 week before challenge and various antigen-induced pulmonary responses were studied. Antigen exposure increased lipid peroxidation in bronchoalveolar lavage fluid (BALF) and oxidised glutathione levels in lung tissue 2 h after challenge. Lung nuclear transcription factor-kappaB-binding activity was increased 2 h after challenge, and BALF tumour necrosis factor-alpha and inducible nitric oxide synthase expression in lungs peaked 4 h after challenge. Expression of intercellular adhesion molecule-1 and mucin MUC5AC was also increased 4 h after challenge. These changes in oxidant status, transcription factor activation, and inflammatory cytokine and gene expression were reduced by N-acetylcysteine. This thiol did not affect the immediate bronchospasm reaction to antigen in anaesthetised rats but inhibited airways hyperresponsiveness to 5-hydroxytryptamine and the augmented eosinophil numbers in BALF, which appear 24 h after exposure of conscious rats to antigen aerosol, and abolished antigen-induced extravasation of Evans blue into BALF.These results indicate that oral N-acetylcysteine exerts an antioxidant protective effect and attenuates pulmonary inflammation in experimental asthma.