Que Loretta G, Liu Limin, Yan Yun, Whitehead Gregory S, Gavett Stephen H, Schwartz David A, Stamler Jonathan S
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Science. 2005 Jun 10;308(5728):1618-21. doi: 10.1126/science.1108228. Epub 2005 May 26.
Mechanisms that protect against asthma remain poorly understood. S-nitrosoglutathione (GSNO), an endogenous bronchodilator, is depleted from asthmatic airways, suggesting a protective role. We report that, following allergen challenge, wild-type mice exhibiting airway hyperresponsivity have increased airway levels of the enzyme GSNO reductase (GSNOR) and are depleted of lung S-nitrosothiols (SNOs). In contrast, mice with genetic deletion of GSNOR exhibit increases in lung SNOs and are protected from airway hyperresponsivity. Our results indicate that endogenous SNOs, governed by GSNOR, are critical regulators of airway responsivity and may provide new therapeutic approaches to asthma.
预防哮喘的机制仍未得到充分了解。内源性支气管扩张剂S-亚硝基谷胱甘肽（GSNO）在哮喘气道中会减少，这表明其具有保护作用。我们报告称，在过敏原激发后，表现出气道高反应性的野生型小鼠气道中GSNO还原酶（GSNOR）水平升高，肺内S-亚硝基硫醇（SNOs）减少。相比之下，GSNOR基因缺失的小鼠肺内SNOs增加，且免受气道高反应性的影响。我们的结果表明，由GSNOR调控的内源性SNOs是气道反应性的关键调节因子，可能为哮喘提供新的治疗方法。
