Smallbone B W, Taylor N E, McDonald J W
Department of Medicine, University of Western Ontario, London, Canada.
J Pharmacol Exp Ther. 1987 Sep;242(3):1035-40.
Thromboxane-mediated pulmonary hypertension, pulmonary edema, arterial hypoxia and pulmonary leukostasis occur in response to the infusion of plasma containing zymosan-activated complement (ZAP) in sheep. Platelet-activating factor (PAF) is a potential mediator of some of these effects. We investigated the effects of PAF infusions in unanesthetized sheep and the effects of the PAF receptor antagonist L-652,731 [trans-2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran] on the hematologic, hemodynamic and biochemical alterations produced by infusions of both ZAP and PAF. Infusions of 2 to 20 micrograms of PAF in 0.25% ovine serum albumin-saline produced pulmonary hypertension, hypoxia and dose-dependent thrombocytopenia, neutropenia and thromboxane synthesis. The effects of a 2 micrograms of PAF infusion were both qualitatively and quantitatively similar to those produced by a ZAP infusion. Pretreatment with aspirin (10 mg/kg) protected the sheep against the pulmonary vascular response to 20 micrograms of PAF and blocked completely the thromboxane synthesis. L-652,731 at a dose of 8 mg/kg blocked completely the neutropenia, thrombocytopenia, thromboxane synthesis, pulmonary hypertension and hypoxia induced by 5 micrograms of PAF, but this protective effect was not observed in animals infused with ZAP. These results indicate that PAF is probably not a mediator of the neutropenia, thromboxane-mediated pulmonary hypertension and hypoxia which result from the infusion of ZAP into sheep.
在绵羊中，输注含有酵母聚糖激活补体（ZAP）的血浆会引发血栓素介导的肺动脉高压、肺水肿、动脉低氧血症和肺白细胞淤滞。血小板活化因子（PAF）可能是其中某些效应的介导物。我们研究了在未麻醉绵羊中输注PAF的效应，以及PAF受体拮抗剂L-652,731[反式-2,5-双（3,4,5-三甲氧基苯基）四氢呋喃]对输注ZAP和PAF所产生的血液学、血流动力学和生化改变的影响。在0.25%绵羊血清白蛋白盐水中输注2至20微克PAF会导致肺动脉高压、低氧血症以及剂量依赖性血小板减少、中性粒细胞减少和血栓素合成。输注2微克PAF所产生的效应在性质和数量上与输注ZAP所产生的效应相似。用阿司匹林（10毫克/千克）预处理可保护绵羊免受20微克PAF引起的肺血管反应，并完全阻断血栓素合成。剂量为8毫克/千克的L-652,731可完全阻断5微克PAF诱导的中性粒细胞减少、血小板减少、血栓素合成、肺动脉高压和低氧血症，但在输注ZAP的动物中未观察到这种保护作用。这些结果表明，PAF可能不是输注ZAP至绵羊体内所导致的中性粒细胞减少、血栓素介导的肺动脉高压和低氧血症的介导物。
