Stokke T, Burchardi H, Hensel I, Hörl W H
Eur J Clin Invest. 1985 Dec;15(6):415-21. doi: 10.1111/j.1365-2362.1985.tb00295.x.
The potential role of granulocyte proteinases on experimentally induced ARDS was evaluated. In order to investigate the acute effects on lung function, elastase (330 U kg-1h-1) or thrombin (75-150 U kg-1 h-1) was continuously infused into anaesthetized and mechanically ventilated mini pigs. Both elastase as well as thrombin induced a progressive respiratory failure with prompt increase in pulmonary vascular resistance, and decrease of cardiac output, further a pulmonary leukostasis, and a disturbance of blood coagulation leading to hypocoagulability. High proteolytic activity selectively in the lung indicates a possible role of proteinases released from sequestered polymorphonuclear neutrophils. Similar results following elastase infusion were however obtained in leukopenic animals pretreated with a single dose of dimethylmyleran (5 mg kg-1) which depleted the granulocytes totally. These results offer the possibility that elastase itself may cause respiratory failure and lung tissue damage. On the other hand the digestion pattern of phosphorylase kinase by lung tissue homogenates of thrombin- or elastase-infused mini pigs clearly indicates that elastase is only one of several mediators which may cause experimentally induced ARDS even in the absence of granulocytes.
评估了粒细胞蛋白酶在实验性诱导的急性呼吸窘迫综合征（ARDS）中的潜在作用。为了研究对肺功能的急性影响，将弹性蛋白酶（330 U kg-1h-1）或凝血酶（75 - 150 U kg-1 h-1）持续输注到麻醉并机械通气的小型猪体内。弹性蛋白酶和凝血酶均诱发进行性呼吸衰竭，伴有肺血管阻力迅速增加、心输出量减少、进而出现肺白细胞淤滞以及导致低凝状态的血液凝固紊乱。肺内选择性的高蛋白水解活性表明，隔离的多形核中性粒细胞释放的蛋白酶可能发挥作用。然而，在用单剂量二甲苯磺酸丁酯（5 mg kg-1）预处理使粒细胞完全耗竭的白细胞减少动物中，输注弹性蛋白酶后也获得了类似结果。这些结果提示弹性蛋白酶本身可能导致呼吸衰竭和肺组织损伤。另一方面，凝血酶或弹性蛋白酶输注的小型猪肺组织匀浆对磷酸化酶激酶的消化模式清楚地表明，即使在没有粒细胞的情况下，弹性蛋白酶也只是可能导致实验性诱导的ARDS的几种介质之一。
