Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice
Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice
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DOI：
10.1152/ajplung.00019.2012
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发表时间：
2012-06-01
影响因子：
4.9
通讯作者：
Mizushima, Tohru
中科院分区：
文献类型：
--
作者：
Tanaka, Ken-Ichiro;Sato, Keizo;Mizushima, Tohru
支气管扩张剂（如异丙托溴铵）、类固醇（如丙酸氟替卡松）和新开发的抗炎药（如罗氟司特）用于慢性阻塞性肺疾病（COPD）患者。我们最近报道，卵磷脂化超氧化物歧化酶（PC-SOD）赋予COPD小鼠模型的保护作用。本文观察了PC-SOD联合异丙托溴铵治疗肺气肿的疗效，并与其他药物进行了比较。通过各种标准评估小鼠肺气肿的严重程度。评估肺力学（弹性）和呼吸功能（前0.05秒用力呼气量与用力肺活量的比值）。吸入PC-SOD可抑制弹性蛋白酶诱导的肺气肿、肺力学改变和呼吸功能障碍。腹腔注射异丙托溴铵不能改变PC-SOD的改善作用。异丙托溴铵、丙酸氟替卡松或罗氟司特单独给药不能像PC-SOD那样有效抑制弹性蛋白酶诱导的肺超氧阴离子水平升高、肺部炎症反应、肺气肿、肺力学改变或呼吸功能障碍。PC-SOD，而不是其他药物，显示了治疗效果，即使在肺气肿发展后给药。PC-SOD还抑制香烟烟雾诱导的肺炎症反应和气道阻力增加。基于这些结果，我们认为吸入PC-SOD对COPD有治疗益处。
Bronchodilators (such as ipratropium bromide), steroids (such as fluticasone propionate), and newly developed anti-inflammatory drugs (such as roflumilast) are used for patients with chronic obstructive pulmonary disease (COPD). We recently reported that lecithinized superoxide dismutase (PC-SOD) confers a protective effect in mouse models of COPD. We here examined the therapeutic effect of the combined administration of PC-SOD with ipratropium bromide on pulmonary emphysema and compared the effect of PC-SOD to other types of drugs. The severity of emphysema in mice was assessed by various criteria. Lung mechanics (elastance) and respiratory function (ratio of forced expiratory volume in the first 0.05 s to forced vital capacity) were assessed. Administration of PC-SOD by inhalation suppressed elastase-induced pulmonary emphysema, alteration of lung mechanics, and respiratory dysfunction. The concomitant intratracheal administration of ipratropium bromide did not alter the ameliorating effects of PC-SOD. Administration of ipratropium bromide, fluticasone propionate, or roflumilast alone did not suppress the elastase-induced increase in the pulmonary level of superoxide anion, pulmonary inflammatory response, pulmonary emphysema, alteration of lung mechanics, or respiratory dysfunction as effectively as did PC-SOD. PC-SOD, but not the other drugs, showed a therapeutic effect even when the drug was administered after the development of emphysema. PC-SOD also suppressed the cigarette smoke-induced pulmonary inflammatory response and increase in airway resistance. Based on these results, we consider that the inhalation of PC-SOD would be therapeutically beneficial for COPD.