Wallace J L, MacNaughton W K
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Eur J Pharmacol. 1988 Jun 22;151(1):43-50. doi: 10.1016/0014-2999(88)90690-5.
The role of leukotriene synthesis in the gastrointestinal damage induced by platelet-activating factor (PAF) was examined in the rat. The effects of a 20-min infusion of PAF (100 ng/kg per min) on leukotriene B4 (LTB4) and leukotriene C4 (LTC4) synthesis were examined in samples of the stomach, duodenum, jejunum, ileum and colon. Administration of PAF resulted in marked hemoconcentration and extensive hemorrhagic damage which was only observed in the corpus region of the stomach and in the small intestine. However, LTB4 synthesis was increased significantly in all regions studied, while LTC4 synthesis was increased significantly only in the duodenum. Pretreatment of the rats with dexamethasone significantly reduced the PAF-induced increase in LTB4 synthesis in all tissues studied. However, a reduction of PAF-induced damage following dexamethasone treatment was observed in the small intestine, but not the stomach. To further investigate the role of leukotrienes as mediators of PAF-induced gastrointestinal damage, the effects of a 10-min infusion of PAF (100 ng/kg per min i.v.) were compared to those of similar infusions of LTB4, LTC4 or leukotriene D4 (LTD4) (0.3-3 micrograms/kg per min). None of the doses of leukotrienes tested produced hemoconcentration or gastrointestinal damage comparable to that observed with the much lower dose of PAF, with the single exception of significant hemoconcentration observed with the highest dose of LTC4. The results of this study therefore suggest that leukotrienes are unlikely to play a major role as mediators of PAF-induced gastrointestinal damage in the rat.
在大鼠中研究了白三烯合成在血小板活化因子（PAF）诱导的胃肠道损伤中的作用。在胃、十二指肠、空肠、回肠和结肠样本中检测了持续输注20分钟的PAF（100纳克/千克每分钟）对白三烯B4（LTB4）和白三烯C4（LTC4）合成的影响。给予PAF导致明显的血液浓缩和广泛的出血性损伤，这种损伤仅在胃体部和小肠中观察到。然而，在所研究的所有区域中LTB4合成均显著增加，而LTC4合成仅在十二指肠中显著增加。用地塞米松预处理大鼠可显著降低在所研究的所有组织中PAF诱导的LTB4合成增加。然而，地塞米松治疗后在小肠中观察到PAF诱导的损伤有所减轻，但在胃中未观察到。为了进一步研究白三烯作为PAF诱导的胃肠道损伤介质的作用，将持续输注10分钟的PAF（100纳克/千克每分钟，静脉注射）的效果与类似输注的LTB4、LTC4或白三烯D4（LTD4）（0.3 - 3微克/千克每分钟）的效果进行了比较。所测试的白三烯剂量均未产生与低得多的PAF剂量所观察到的相当的血液浓缩或胃肠道损伤，唯一的例外是最高剂量的LTC4观察到明显的血液浓缩。因此，本研究结果表明白三烯不太可能在大鼠中作为PAF诱导的胃肠道损伤的主要介质发挥作用。
