Sakuma T, Takahashi K, Ohya N, Usuda K, Handa M, Abe T
Department of Respiratory Medicine, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Eur J Pharmacol. 1998 Jul 24;353(2-3):273-9. doi: 10.1016/s0014-2999(98)00412-9.
The imbalance of neutrophil elastase and alpha1-antitrypsin in pleural effusion after lobectomy and the effects of the neutrophil elastase inhibitors, sodium N-[2-[4-(2,2-Dimethylpropionyloxy)phenyl-sulfonylamino]benzo yl]aminoacetic acid (ONO-5046) and purified alpha1-antitrypsin, on neutrophil elastase activity were determined. The amount of neutrophil elastase complexed to alpha1-antitrypsin, measured by an enzyme-linked immunosorbent assay, was 170 times higher in pleural effusion than in blood 3 h after lobectomy. The alpha1-antitrypsin levels measured by laser nephelometry did not increase in either blood or pleural effusion. Although neutrophil elastase activity, measured by the hydrolysis of succinyl-(Ala)3-p-nitroanilide, was not detected in blood, it was increased in pleural effusion 3 h and 24 h after lobectomy. ONO-5046, but not alpha1-antitrypsin, reduced the neutrophil elastase activity in pleural effusion. There is an imbalance of neutrophil elastase and alpha1-antitrypsin in pleural effusion after lobectomy. ONO-5046 is a potent inhibitor of neutrophil elastase activity in human pleural effusion.
测定了肺叶切除术后胸腔积液中中性粒细胞弹性蛋白酶与α1-抗胰蛋白酶的失衡情况，以及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)苯基磺酰氨基]苯甲酰基]氨基乙酸钠（ONO-5046）和纯化的α1-抗胰蛋白酶对中性粒细胞弹性蛋白酶活性的影响。通过酶联免疫吸附测定法测得，肺叶切除术后3小时，胸腔积液中与α1-抗胰蛋白酶结合的中性粒细胞弹性蛋白酶量比血液中高170倍。通过激光散射比浊法测得的α1-抗胰蛋白酶水平在血液和胸腔积液中均未升高。虽然通过琥珀酰-(丙氨酸)3-对硝基苯胺水解法测得的中性粒细胞弹性蛋白酶活性在血液中未检测到，但在肺叶切除术后3小时和24小时的胸腔积液中有所升高。ONO-5046可降低胸腔积液中的中性粒细胞弹性蛋白酶活性，而α1-抗胰蛋白酶则无此作用。肺叶切除术后胸腔积液中存在中性粒细胞弹性蛋白酶与α1-抗胰蛋白酶的失衡。ONO-5046是人类胸腔积液中中性粒细胞弹性蛋白酶活性的有效抑制剂。
