特异性中性粒细胞弹性蛋白酶抑制剂ONO-5046对佛波酯肉豆蔻酸酯乙酸酯诱导的离体犬肺损伤的影响。

Effect of ONO-5046, a specific neutrophil elastase inhibitor, on the phorbol myristate acetate-induced injury in isolated dog lung.

作者信息

Wang H G, Shibamoto T, Miyahara T, Haniu H, Tanaka S, Fujimoto K, Honda T, Kubo K, Koyama S

机构信息

Department of Physiology, Shinshu University of Medicine, Matsumoto, Japan.

出版信息

Exp Lung Res. 1999 Jan-Feb;25(1):55-67. doi: 10.1080/019021499270420.

DOI:10.1080/019021499270420

PMID:10027079

Abstract

Phorbol myristate acetate (PMA) activates neutrophils and causes acute lung injury. We determined the effect of ONO-5046, a specific neutrophil elastase inhibitor, on the increase in microvascular permeability induced by PMA in isolated dog lung perfused with autologous blood at a constant perfusion flow. The vascular permeability was assessed by the capillary filtration coefficient (Kf, c) and the solvent-drag reflection coefficient (sigma f). PMA (13.3 micrograms) increased vascular permeability, as evidenced by an increase in Kf, c from 0.18 +/- 0.02 to 0.92 +/- 0.14 mL/min/cmH2O/100 g and a decrease in sigma f to 0.35 +/- 0.01 as compared to control values of 0.69 +/- 0.06. The PMA-induced changes in Kf, c and sigma f were dose-dependently attenuated by pretreatment with ONO-5046 (2-20 mg). We conclude that ONO-5046 can effectively attenuate the PMA-induced injury in the isolated blood-perfused dog lungs.

摘要

佛波醇肉豆蔻酸酯乙酸盐（PMA）可激活中性粒细胞并导致急性肺损伤。我们测定了特异性中性粒细胞弹性蛋白酶抑制剂ONO - 5046对在以恒定灌注流量灌注自体血的离体犬肺中由PMA诱导的微血管通透性增加的影响。通过毛细血管滤过系数（Kf，c）和溶剂拖曳反射系数（sigma f）评估血管通透性。PMA（13.3微克）增加了血管通透性，Kf，c从0.18±0.02增加到0.92±0.14 mL/分钟/厘米水柱/100克，sigma f降至0.35±0.01，而对照值为0.69±0.06，证明了这一点。用ONO - 5046（2 - 20毫克）预处理可剂量依赖性地减弱PMA诱导的Kf，c和sigma f变化。我们得出结论，ONO - 5046可有效减轻离体血液灌注犬肺中PMA诱导的损伤。