Inhibition of neutrophil elastase activity attenuates complement-mediated lung injury in the hamster
Inhibition of neutrophil elastase activity attenuates complement-mediated lung injury in the hamster
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DOI：
10.1016/s0014-2999(01)01191-8
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发表时间：
2001-08-24
影响因子：
5
通讯作者：
Ohno, H
中科院分区：
文献类型：
--
作者：
Hagio, T;Nakao, S;Ohno, H
使用特异性中性粒细胞弹性蛋白酶抑制剂N-[2-[4-（2，2二甲基丙酰氧基）苯磺酰氨基]苯甲酰基]氨基乙酸钠四水合物（西维来司他），在仓鼠中检查中性粒细胞弹性蛋白酶在补体介导的肺损伤中的作用。静脉注射眼镜蛇毒因子（CVF）到仓鼠中瞬时增加血浆中性粒细胞弹性蛋白酶活性约10倍。该增加之后，肺血管[I-125]牛血清白蛋白渗透性持续增加，在CVF注射后30分钟达到峰值。肺血管通透性的增加与肺组织中中性粒细胞蓄积和支气管肺泡灌洗液中蛋白浓度的增加有关。通过连续静脉输注西维来司他（0.1、0.3和1 mg/kg/h）抑制血浆中性粒细胞弹性蛋白酶活性升高（36.5%、66.9%和104.3%），剂量依赖性地减弱CVF注射后30 min肺血管通透性的增加。此外，1 mg/kg/h的西维来司他几乎完全阻止了支气管肺泡灌洗液中蛋白质浓度的增加，而不影响肺部中性粒细胞积聚。这些结果表明，中性粒细胞弹性蛋白酶是补体介导的急性肺损伤的重要介质。(C)2001爱思唯尔科技有限公司。保留所有权利。
The role of neutrophil elastase in complement-mediated lung injury was examined in hamsters using a specific neutrophil elastase inhibitor, sodium N-[2-[4-(2,2 dimethylpropionyloxy)phenylsulfonylamino]benzoyl]aminoacetate tetrahydrate (sivelestat). Intravenous injection with cobra venom factor (CVF) into hamsters transiently increased plasma neutrophil elastase activity by about 10-fold. This increase was followed by a sustained increase in lung vascular [I-125]bovine serum albumin permeability peaking 30 min after CVF injection. The increase in lung vascular permeability was associated with neutrophil accumulation in lung tissue and an increase in protein concentration in the bronchoalveolar lavage fluid. Inhibition of the elevated plasma neutrophil elastase activity (36.5%, 66.9% and 104.3%) by continuous i.v. infusion with sivelestat (0.1, 0.3 and 1 mg/kg/h), dose-dependently attenuated the increase in lung vascular permeability 30 min after CVF injection. Furthermore, sivelestat at 1 mg/kg/h almost totally prevented the increase in protein concentration in the bronchoalveolar lavage fluid without affecting lung neutrophil accumulation. These results suggest that neutrophil elastase is an important mediator in complement-mediated acute lung injury. (C) 2001 Elsevier Science B.V. All rights reserved.