Therapeutic Effect of Lecithinized Superoxide Dismutase on Pulmonary Emphysema
Therapeutic Effect of Lecithinized Superoxide Dismutase on Pulmonary Emphysema
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DOI：
10.1124/jpet.111.179051
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发表时间：
2011-09-01
影响因子：
3.5
通讯作者：
Mizushima, Tohru
中科院分区：
文献类型：
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作者：
Tanaka, Ken-Ichiro;Tanaka, Yuta;Mizushima, Tohru
目前还没有药物能明显改善慢性阻塞性肺疾病（COPD）的死亡率。氧化分子，特别是超氧阴离子，在COPD相关的异常炎症反应和肺气肿中起重要作用，这是由于蛋白酶和抗蛋白酶失衡以及细胞凋亡增加而引起的。超氧化物歧化酶（SOD）催化超氧阴离子歧化。卵磷脂化的人Cu/Zn-SOD（PC-SOD）克服了SOD的许多临床局限性，包括低组织亲和力和在血浆中的低稳定性。在这项研究中，我们研究了PC-SOD对弹性蛋白酶诱导的肺气肿，COPD动物模型的影响。通过各种标准评估小鼠肺部炎症反应和肺气肿的严重程度，例如支气管肺泡灌洗液中的白细胞数量和空气空间的扩大。不仅静脉给药，而且吸入PC-SOD抑制弹性蛋白酶诱导的肺部炎症，肺气肿和功能障碍。吸入PC-SOD抑制弹性蛋白酶诱导的肺超氧阴离子水平和细胞凋亡的增加。吸入PC-SOD还抑制弹性蛋白酶诱导的蛋白酶活化，并降低抗蛋白酶水平和促炎细胞因子和趋化因子的表达。我们还发现，吸入PC-SOD抑制香烟烟雾引起的肺部炎症。结果表明，PC-SOD通过降低肺组织超氧阴离子水平，抑制炎症反应和细胞凋亡，改善蛋白酶/抗蛋白酶失衡，从而保护肺气肿。我们认为吸入PC-SOD对COPD有治疗益处。
No medication exists that clearly improves the mortality of chronic obstructive pulmonary disease (COPD). Oxidative molecules, in particular superoxide anions, play important roles in the COPD-associated abnormal inflammatory response and pulmonary emphysema, which arises because of an imbalance in proteases and antiproteases and increased apoptosis. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide anions. Lecithinized human Cu/Zn- SOD (PC-SOD) has overcome a number of the clinical limitations of SOD, including low tissue affinity and low stability in plasma. In this study, we examine the effect of PC-SOD on elastase-induced pulmonary emphysema, an animal model of COPD. The severity of the pulmonary inflammatory response and emphysema in mice was assessed by various criteria, such as the number of leukocytes in the bronchoalveolar lavage fluid and the enlargement of airspace. Not only intravenous administration but also inhalation of PC-SOD suppressed elastase-induced pulmonary inflammation, emphysema, and dysfunction. Inhalation of PC-SOD suppressed the elastase-induced increase in the pulmonary level of superoxide anions and apoptosis. Inhalation of PC-SOD also suppressed elastase-induced activation of proteases and decreased in the level of antiproteases and expression of proinflammatory cytokines and chemokines. We also found that inhalation of PC-SOD suppressed cigarette smoke-induced pulmonary inflammation. The results suggest that PC-SOD protects against pulmonary emphysema by decreasing the pulmonary level of superoxide anions, resulting in the inhibition of inflammation and apoptosis and amelioration of the protease/antiprotease imbalance. We propose that inhalation of PC-SOD would be therapeutically beneficial for COPD.