Effects of Lecithinized Superoxide Dismutase and/or Pirfenidone Against Bleomycin-Induced Pulmonary Fibrosis
Effects of Lecithinized Superoxide Dismutase and/or Pirfenidone Against Bleomycin-Induced Pulmonary Fibrosis
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DOI：
10.1378/chest.11-2879
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发表时间：
2012-10-01
期刊：
影响因子：
9.6
通讯作者：
Mizushima, Tohru
中科院分区：
文献类型：
--
作者：
Tanaka, Ken-Ichiro;Azuma, Arata;Mizushima, Tohru
背景：特发性肺纤维化(IPF)涉及超氧阴离子等活性氧自由基(ROS)引起的肺损伤和纤维化。超氧化物歧化酶(SOD)催化超氧阴离子歧化为过氧化氢。我们最近报道，吸入卵磷脂超氧化物歧化酶(PC-SOD)可改善博莱霉素所致的肺纤维化。我们研究了PC-SOD对博莱霉素性肺纤维化和肺功能障碍的影响，并与新药吡非尼酮进行了比较。方法：用计算机控制的呼吸机测定肺弹性和呼吸功能。通过监测经皮动脉血氧饱和度(Spo(2))评价呼吸功能。结果：吸入PC-SOD和口服吡非尼酮均能减轻博莱霉素性肺纤维化和肺力学改变。博莱霉素组FVC和Spo(2)均降低。PC-SOD治疗使这两个参数显著恢复，而吡非尼酮仅改善Spo(2)。PC-SOD比吡非尼酮更有效地抑制博莱霉素诱导的肺炎症反应和肺内超氧阴离子的产生。此外，PC-SOD和吡非尼酮都产生了治疗效果，即使是在纤维化发生后给予该药也是如此。PC-SOD与吡非尼酮也具有协同治疗作用。结论：PC-SOD抗博莱霉素性肺纤维化和肺功能障碍的作用优于吡非尼酮，其机制可能与其独特的抗氧化活性有关。我们认为联合应用PC-SOD和吡非尼酮治疗IPF可能是有益的。《胸腔》2012；142(4)：1011-1019
Background: Idiopathic pulmonary fibrosis (IPF) involves lung injury induced by reactive oxygen species (ROS), such as superoxide anion, and fibrosis. Superoxide dismutase (SOD) catalyses the dismutation of superoxide anion to hydrogen peroxide. We recently reported that inhalation of lecithinized SOD (PC-SOD) ameliorated bleomycin-induced pulmonary fibrosis. We here studied effects of PC-SOD on bleomycin-induced pulmonary fibrosis and lung dysfunction and compared the results to those obtained with pirfenidone, a newly developed drug for IPF.Methods: Lung mechanics (elastance) and respiratory function (FVC) were assessed using a computer-controlled ventilator. Respiratory function was evaluated by monitoring percutaneous arterial oxygen saturation (Spo(2)).Results: Both inhalation of PC-SOD and oral administration of pirfenidone ameliorated bleomycin-induced pulmonary fibrosis and changes in lung mechanics. Administration of bleomycin produced a decrease in both FVC and Spo(2). PC-SOD treatment led to significant recovery of both parameters, whereas pirfenidone improved only Spo(2). PC-SOD suppressed the bleomycin-induced pulmonary inflammatory response and production of superoxide anions in the lung more effectively than pirfenidone. Furthermore, both PC-SOD and pirfenidone produced a therapeutic effect even when the drug was administered after the development of fibrosis. PC-SOD and pirfenidone also produced a synergistic therapeutic effect.Conclusions: These results suggest that the superior activity of PC-SOD to pirfenidone against bleomycin-induced pulmonary fibrosis and lung dysfunction is due to its unique antioxidant activity. We propose that treatment of IPF with a combination of PC-SOD and pirfenidone could be therapeutically beneficial. CHEST 2012; 142(4):1011-1019