Effects of edaravone, a free-radical scavenger, on bleomycin-induced lung injury in mice
Effects of edaravone, a free-radical scavenger, on bleomycin-induced lung injury in mice
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DOI：
10.1183/09031936.00164407
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发表时间：
2008-11
影响因子：
24.3
通讯作者：
S. Tajima;M. Bando;Yoshiki Ishii;T. Hosono;H. Yamasawa;S. Ohno;T. Takada;E. Suzuki;Fumitake Gejyo;Yukihiko Sugiyama
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文献类型：
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作者：
S. Tajima;M. Bando;Yoshiki Ishii;T. Hosono;H. Yamasawa;S. Ohno;T. Takada;E. Suzuki;Fumitake Gejyo;Yukihiko Sugiyama
活性氧在急性肺损伤和肺纤维化的发病机制中起重要作用。本研究假设自由基清除剂依达拉奉可通过降低氧化应激来减轻博莱霉素(BLM)所致的小鼠肺损伤。−-1 5 mg·kg-1气管内滴注诱导雌性ICR小鼠肺损伤。依达拉奉(30 0 mg·kg-1，−-1)于造模前1h给予依达拉奉。依达拉奉可使BLM组小鼠存活率从25%提高到90%，第7天BALF中细胞总数和中性粒细胞数减少，第2天BALF和血清中脂质过氧化氢含量降低。组织学检查和羟脯氨酸含量测定显示，28天时肺纤维化明显减轻。此外，依达拉奉在第2天显著增加BALF中前列腺素E_2的浓度。综上所述，依达拉奉可通过抑制脂质过氧化氢的产生和增加前列腺素E_2的产生来抑制肺损伤和纤维化。
Reactive oxygen species play an important role in the pathogenesis of acute lung injury and pulmonary fibrosis. The present authors hypothesise that edaravone, a free-radical scavenger, is able to attenuate bleomycin (BLM)-induced lung injury in mice by decreasing oxidative stress. Lung injury was induced in female ICR mice by intratracheal instillation of 5 mg·kg−1 of BLM. Edaravone (300 mg·kg−1) was administered by intraperitoneal administration 1 h before BLM challenge. Edaravone significantly improved the survival rate of mice treated with BLM from 25 to 90%, reduced the number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) on day 7, and attenuated the concentrations of lipid hydroperoxide in BALF and serum on day 2. The fibrotic change in the lung on day 28 was ameliorated by edaravone, as evaluated by histological examination and measurement of hydroxyproline contents. In addition, edaravone significantly increased the prostaglandin E2 concentration in BALF on day 2. In summary, edaravone was shown to inhibit lung injury and fibrosis via the repression of lipid hydroperoxide production and the elevation of prostaglandin E2 production in the present experimental murine system.