Olson N C, Dobrowsky R T, Fleisher L N
Department of Anatomy, School of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Prostaglandins Leukot Essent Fatty Acids. 1988 May;32(2):57-62. doi: 10.1016/0952-3278(88)90096-8.
We hypothesized that leukotriene B4 (LTB4) might be produced during endotoxin-induced acute respiratory failure (ARF) observed in young pigs. We used radioimmunoassay (RIA) and reverse phase-high performance liquid chromatography (RP-HPLC) to determine the presence of LTB4 in plasma and bronchoalveolar lavage fluid (BALF) of saline- and endotoxin-treated pigs. Endotoxin was infused at 5 micrograms/kg for 1 hour (hr) followed by 2 micrograms/kg/hr for an average of 3 hrs. Arterial plasma (collected at 0.5 hr intervals for 4 hrs) immunoreactive (i)-LTB4 was significantly increased from 2.5 to 4 hrs of endotoxemia with the peak value occurring at 3.5 hrs (i.e. 282% of baseline value). Analysis of plasma extracts using RP-HPLC revealed an ultraviolet (UV) absorbance peak (270 nm) that was coincident with authentic LTB4 standard. The levels of i-LTB4 were significantly increased in BALF recovered from endotoxemic pigs (337 +/- 71 vs 53 +/- 13 pg/ml for saline controls). Endotoxin also increased the postmortem wet/dry ratio of bloodless lung and BALF albumin concentration, indicating pulmonary edema and increased permeability of the alveolar-capillary membrane, respectively. We conclude that LTB4 is increased in plasma and BALF recovered from endotoxemic pigs and that this lipoxygenase metabolite could possibly be an important factor contributing to the pathophysiology of endotoxin-induced ARF.
我们推测，在幼猪内毒素诱导的急性呼吸衰竭（ARF）过程中可能会产生白三烯B4（LTB4）。我们采用放射免疫分析法（RIA）和反相高效液相色谱法（RP-HPLC）来测定生理盐水处理组和内毒素处理组猪血浆及支气管肺泡灌洗液（BALF）中LTB4的存在情况。以5微克/千克的剂量输注内毒素1小时，随后以2微克/千克/小时的剂量输注，平均持续3小时。动脉血浆（每隔0.5小时采集4小时）中免疫反应性（i）-LTB4在内毒素血症发生后2.5至4小时显著升高，峰值出现在3.5小时（即基线值的282%）。使用RP-HPLC对血浆提取物进行分析，发现一个紫外线（UV）吸收峰（270纳米），该峰与标准LTB4一致。从内毒素血症猪回收的BALF中i-LTB4水平显著升高（生理盐水对照组为53±13皮克/毫升，内毒素血症组为337±71皮克/毫升）。内毒素还增加了无血肺的死后湿/干比和BALF白蛋白浓度，分别表明肺水肿和肺泡-毛细血管膜通透性增加。我们得出结论，内毒素血症猪的血浆和BALF中LTB4升高，这种脂氧合酶代谢产物可能是内毒素诱导的ARF病理生理学的一个重要因素。
