Chang S W, Feddersen C O, Henson P M, Voelkel N F
J Clin Invest. 1987 May;79(5):1498-509. doi: 10.1172/JCI112980.
Within 20 min after intraperitoneal injection of Salmonella enteritidis endotoxin in rats, blood platelet-activating factor (PAF) increased from 4.3 +/- 1.3 to 13.7 +/- 2.0 ng/ml (P less than 0.01) and lung PAF from 32.3 +/- 4.9 to 312.3 +/- 19.6 ng (P less than 0.01), but not lung lavage PAF. We tested the effect of PAF receptor antagonists, CV 3988 and SRI 63-441, on endotoxin-induced hemodynamic changes and lung vascular injury. Pretreatment with CV 3988 attenuated systemic hypotension, preserved hypoxic pulmonary vasoconstriction, and prolonged survival of awake catheter-implanted endotoxin-treated (20 mg/kg) rats. Pretreatment with SRI 63-441 prevented the depressed hypoxic pulmonary vasoconstriction after low dose (2 mg/kg) endotoxin. Both CV 3988 and SRI 63-441 blocked the increased extravascular accumulation of 125I-albumin and water in perfused lungs isolated from endotoxin-treated rats. We conclude that PAF is produced in the lung during endotoxemia and may be an important mediator of the systemic and pulmonary hemodynamic changes as well as the acute lung vascular injury after endotoxemia.
给大鼠腹腔注射肠炎沙门氏菌内毒素后20分钟内，血小板活化因子（PAF）从4.3±1.3 ng/ml增加至13.7±2.0 ng/ml（P<0.01），肺PAF从32.3±4.9 ng增加至312.3±19.6 ng（P<0.01），但肺灌洗PAF未增加。我们测试了PAF受体拮抗剂CV 3988和SRI 63-441对内毒素诱导的血流动力学变化和肺血管损伤的影响。用CV 3988预处理可减轻全身低血压，保留低氧性肺血管收缩，并延长清醒状态下植入导管的内毒素处理（20 mg/kg）大鼠的存活时间。用SRI 63-441预处理可预防低剂量（2 mg/kg）内毒素后低氧性肺血管收缩的抑制。CV 3988和SRI 63-441均可阻断从内毒素处理大鼠分离的灌注肺中125I-白蛋白和水的血管外蓄积增加。我们得出结论，内毒素血症期间肺中会产生PAF，PAF可能是内毒素血症后全身和肺血流动力学变化以及急性肺血管损伤的重要介质。
