Sivelestat, a specitic neutrophil elastase inhibitor, prevented phorbol myristate acetate-induced acute lung injury in conscious rabbits
Sivelestat, a specitic neutrophil elastase inhibitor, prevented phorbol myristate acetate-induced acute lung injury in conscious rabbits
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DOI：
10.1016/j.pupt.2004.12.013
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Kawabata, K
中科院分区：
文献类型：
--
作者：
Hagio, T;Matsumoto, S;Kawabata, K
中性粒细胞弹性蛋白酶（NE）在佛波酯（PMA）诱导的急性肺损伤中的作用目前尚不清楚。本研究使用特异性NE抑制剂西维来司他钠水合物（西维来司他）检查NE在清醒家兔PMA诱导的急性肺损伤中的作用。单次推注PMA（40 μ g/kg）引起急性肺损伤，表现为注射PMA后4 h支气管肺泡灌洗液（BALF）中蛋白质浓度增加和出血。这些变化与动脉血氧分压和外周白色血细胞和血小板轻度降低有关。当在PMA注射前1小时开始并在PMA注射后4小时结束时连续输注能够抑制兔NE活性60- 90%的3-30 mg/kg/h的西维来司特时，剂量依赖性地减轻PMA诱导的出血性肺炎和BALF中蛋白浓度的增加，而不影响肺中的髓过氧化物酶活性。组织病理学研究表明，西维来司他（30 mg/kg/h）可明显减轻肺组织病理学改变、肺泡出血和白色血细胞迁移，并抑制BALF中NE活性。这些结果表明，NE在PMA诱导的急性肺损伤中起着重要作用，并进一步支持了这种酶在急性肺损伤中的重要性。(c)2005爱思唯尔有限公司保留所有权利。
The in vivo contribution of neutrophil elastase (NE) in phorbol myristate acetate (PMA)-induced acute lung injury has so far been unclear. This study examined the role of NE in PMA-induced acute lung injury in conscious rabbits, using a specific NE inhibitor, sivelestat sodium hydrate (Sivelestat). A single bolus injection of PMA (40 mu g/kg) caused acute lung injury as indicated by an increase in protein concentration and hemorrhage in bronchoalveolar lavage fluid (BALF) 4 h after PMA injection. These changes were associated with mild decrease in arterial oxygen pressure and peripheral white blood cell and platelet. When continuously infused starting 1 h before and ending 4 h post-PMA injection, Sivelestat at 3-30 mg/kg/h that are able to inhibit rabbit NE activity by 60-90%, dose-dependently attenuated both PMA-induced hemorrhagic pneumonitis and the increase in protein concentration in BALF without affecting myeloperoxidase activity in the lung. Histopathological study indicated that sivelestat (30 mg/kg/h) markedly attenuated lung histopathological changes, alveolar hemorrhage and white blood cells migration with evidence of inhibition of NE activity in BALF. These results suggest that NE plays a significant role in PMA-induced acute lung injury and further supports the importance of this enzyme in acute lung injury. (c) 2005 Elsevier Ltd. All rights reserved.