Therapeutic effect of lecithinized superoxide dismutase on bleomycin-induced pulmonary fibrosis
Therapeutic effect of lecithinized superoxide dismutase on bleomycin-induced pulmonary fibrosis
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DOI：
10.1152/ajplung.00289.2009
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发表时间：
2010-03-01
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;Ishihara, Tomoaki;Mizushima, Tohru
田中科，石原，石原，阿祖马，Kudoh S，伊碧娜M， Nukiwa T, Sugiyama Y, Tasaka Y, Namba T，石原T， Sato K, Mizushima Y, Mizushima T.卵磷脂化超氧化物歧化酶对博莱霉素诱导肺纤维化的治疗作用。[J] .中国生物医学工程学报，2016,31(4):349 - 356。首次发表于2009年12月24日；doi: 10.1152 / ajplung.00289.2009。特发性肺纤维化（IPF）被认为与白细胞的炎症浸润、活性氧（ROS），特别是超氧阴离子诱导的肺损伤和纤维化（胶原沉积）有关。目前还没有任何治疗方法能明确改善IPF患者的预后。超氧化物歧化酶（SOD）催化超氧化物阴离子分解成过氧化氢，过氧化氢随后被过氧化氢酶解毒。卵磷脂化超氧化物歧化酶（PC-SOD）克服了超氧化物歧化酶的临床局限性，包括低组织亲和力和低血浆稳定性。在本研究中，我们检测了PC-SOD对博莱霉素诱导的肺纤维化的影响。通过各种方法评估博来霉素诱导的小鼠纤维化的严重程度，包括测定肺组织中的羟脯氨酸水平。静脉给药PC-SOD可抑制博莱霉素诱导的支气管肺泡灌洗液中白细胞数量的增加。PC-SOD也抑制了博莱霉素诱导的胶原沉积和肺中羟脯氨酸水平的升高，提示PC-SOD抑制博莱霉素诱导的肺纤维化。PC-SOD的剂量-反应曲线呈钟形，但同时给药过氧化氢酶恢复了高剂量PC-SOD的改善效果。气管内给药或吸入PC-SOD也能减轻博莱霉素引起的炎症反应和纤维化。这些给药途径未观察到PC-SOD的钟形剂量反应谱。我们认为，与静脉给药相比，吸入PC-SOD可能是一种更有益的给药途径，因为使用该药物治疗的患者具有更高的安全性和生活质量。
Tanaka K, Ishihara T, Azuma A, Kudoh S, Ebina M, Nukiwa T, Sugiyama Y, Tasaka Y, Namba T, Ishihara T, Sato K, Mizushima Y, Mizushima T. Therapeutic effect of lecithinized superoxide dismutase on bleomycin-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 298: L348-L360, 2010. First published December 24, 2009; doi:10.1152/ajplung.00289.2009.-Idiopathic pulmonary fibrosis (IPF) is thought to involve inflammatory infiltration of leukocytes, lung injury induced by reactive oxygen species (ROS), in particular superoxide anion, and fibrosis (collagen deposition). No treatment has been shown to improve definitively the prognosis for IPF patients. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide anion to hydrogen peroxide, which is subsequently detoxified by catalase. Lecithinized SOD (PC-SOD) has overcome clinical limitations of SOD, including low tissue affinity and low stability in plasma. In this study, we examined the effect of PC-SOD on bleomycin-induced pulmonary fibrosis. Severity of the bleomycin-induced fibrosis in mice was assessed by various methods, including determination of hydroxyproline levels in lung tissue. Intravenous administration of PC-SOD suppressed the bleomycin-induced increase in the number of leukocytes in bronchoalveolar lavage fluid. Bleomycin-induced collagen deposition and increased hydroxyproline levels in the lung were also suppressed in animals treated with PC-SOD, suggesting that PC-SOD suppresses bleomycin-induced pulmonary fibrosis. The dose-response profile of PC-SOD was bell-shaped, but concurrent administration of catalase restored the ameliorative effect at high doses of PC-SOD. Intratracheal administration or inhalation of PC-SOD also attenuated the bleomycin-induced inflammatory response and fibrosis. The bell-shaped dose-response profile of PC-SOD was not observed for these routes of administration. We consider that, compared with intravenous administration, inhalation of PC-SOD may be a more therapeutically beneficial route of administration due to the higher safety and quality of life of the patient treated with this drug.