Longo W E, Polities G, Vernava A M, Deshpande Y, Niehoff M, Chandel B, Kulkarni A, Kaminski D L
Department of Surgery, St Louis University School of Medicine, Missouri 63110-0250.
Prostaglandins Leukot Essent Fatty Acids. 1994 Dec;51(6):419-24. doi: 10.1016/0952-3278(94)90059-0.
Platelet-activating factor (PAF) is an endogenous phospholipid which may be an important mediator of shock and inflammation. Recent evidence suggests that PAF plays a role in the development of ischemic colitis and inflammatory bowel disease. Its effects are mediated by second messengers, including the arachidonic acid metabolites. Using an ex vivo isolated left colon rabbit perfusion model, our aims were to determine whether exogenously administered trinitrobenzene sulfonic acid (TNB), which produces experimental colitis, stimulates both PAF and eicosanoid release in the colon, and if so, whether this effect can be blocked by a PAF antagonist. Colonic inflammation was induced by the intracolonic administration of 0.25 ml of 50% ethanol containing 30 mg of TNB. Tissue and perfusate concentrations of the eicosanoids, [prostaglandin E (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2), leukotriene B4 (LTB4)] and the autocoid PAF were measured by ELISA. During TNB infusion there was a significant increase in tissue levels of PAF compared to control colons. Additional studies performed pretreating the colons with the PAF receptor antagonist WEB-2170 prior to TNB infusion blocked PAF release. TNB stimulated release of luminal eicosanoids except LTB4 and suppressed release of tissue prostanoids. Pretreatment with WEB-2170 prior to TNB inhibited luminal eicosanoids, and inhibited PGE2 and prostacyclin, but not TX tissue suppression. Inhibition of TNB-stimulated PAF release by WEB-2170 suggests that PAF may play a role in TNB-induced colitis and this phenomenon may mediate tissue injury.
血小板活化因子（PAF）是一种内源性磷脂，可能是休克和炎症的重要介质。最近的证据表明，PAF在缺血性结肠炎和炎症性肠病的发展中起作用。其作用由第二信使介导，包括花生四烯酸代谢产物。使用离体分离的左结肠兔灌注模型，我们的目的是确定外源性给予产生实验性结肠炎的三硝基苯磺酸（TNB）是否会刺激结肠中PAF和类花生酸的释放，如果是，这种作用是否可以被PAF拮抗剂阻断。通过结肠内给予0.25 ml含30 mg TNB的50%乙醇诱导结肠炎症。通过酶联免疫吸附测定法测量类花生酸[前列腺素E（PGE2）、6-酮-前列腺素F1α（6-酮-PGF1α）和血栓素B2（TXB2）、白三烯B4（LTB4）]和自分泌物质PAF的组织和灌注液浓度。与对照结肠相比，在输注TNB期间，PAF的组织水平显著增加。在输注TNB之前用PAF受体拮抗剂WEB-2170预处理结肠的额外研究阻断了PAF的释放。TNB刺激除LTB4外的腔内类花生酸释放，并抑制组织前列腺素的释放。在TNB之前用WEB-2170预处理可抑制腔内类花生酸，并抑制PGE2和前列环素，但不抑制TX组织抑制。WEB-2170对TNB刺激的PAF释放的抑制表明，PAF可能在TNB诱导的结肠炎中起作用，并且这种现象可能介导组织损伤。
