Hubbard J D, Janssen H F
Department of Physiology, Texas Tech University Health Sciences Center, Lubbock.
Circ Shock. 1988 Oct;26(2):169-83.
The ability of sodium ibuprofen to prevent endotoxin-induced changes in vascular permeability was examined in an anesthetized canine model. Ibuprofen was administered i.v. (3.75 mg/kg) in two pretreatment doses before the administration of Escherichia coli endotoxin (0.5 mg/kg). Serum and left thoracic duct lymph samples were collected for measurement of total protein and separation by polyacrylamide gel electrophoresis. Four protein fractions with molecular weights (MW) ranging from 60,000 to 1,000,000 were consistently analyzed. Administration of endotoxin alone resulted in hypotension and was accompanied by an increase in microvascular permeability as evidenced by increases in lymph flow rate, protein flux, lymph/plasma protein ratio (L/P), and permeability-surface area product (PS). Pretreatment with ibuprofen attenuated the increase in permeability as reflected by significantly lower lymph flow rate, protein flux, L/P, and PS. Electrophoretic data illustrate partial to complete protection for all four MW fractions. These results suggest that endotoxin damages microvascular integrity and increases extravasation of macromolecules as great as 1,000,000 MW. This damage is attenuated significantly by pretreatment with ibuprofen.
在麻醉犬模型中研究了布洛芬钠预防内毒素诱导的血管通透性变化的能力。在给予大肠杆菌内毒素（0.5mg/kg）之前，静脉注射布洛芬（3.75mg/kg），分两个预处理剂量给药。收集血清和左胸导管淋巴样本用于测量总蛋白，并通过聚丙烯酰胺凝胶电泳进行分离。始终分析分子量（MW）范围为60,000至1,000,000的四个蛋白组分。单独给予内毒素导致低血压，并伴有微血管通透性增加，这通过淋巴流速、蛋白通量、淋巴/血浆蛋白比率（L/P）和通透表面积乘积（PS）的增加得到证明。布洛芬预处理减弱了通透性的增加，这表现为淋巴流速、蛋白通量、L/P和PS显著降低。电泳数据表明对所有四个MW组分有部分至完全的保护作用。这些结果表明，内毒素会损害微血管完整性，并增加高达1,000,000MW的大分子外渗。布洛芬预处理可显著减轻这种损害。
