Wang Y, Mitchell J, Sharma M, Gabriel A, Moriyama K, Palmer P Pierce
Department of Anesthesia and Perioperative Care, University of California, 513 Parnassus Avenue, San Francisco, California 94143, USA.
Inflamm Res. 2004 Feb;53(2):66-71. doi: 10.1007/s00011-003-1224-2. Epub 2004 Jan 26.
The aim of this study was to investigate whether leukotrienes synthesized by 5-lipoxygenase (5-LO) and acting via leukotriene (LT) receptors contribute to 5-hydroxytryptamine (5-HT)-induced knee joint plasma extravasation (PE).
Knee joints of rats under anesthesia were perfused with 5-HT and synovial vascular Evans Blue dye leakage was measured spectrophotometrically. A series of 5-LO inhibitors and LT receptor antagonists were investigated for their ability to inhibit 5-HT-induced synovial PE.
Inhibitors of 5-LO (NDGA and REV 5901) significantly attenuated 5-HT-induced plasma extravasation. MK 571, LY 171883, BAY u9773 (CysLT receptor antagonists) and REV 5901 (a CysLT receptor antagonist and a 5-LO inhibitor) were equally effective in inhibiting 5-HT-induced PE, indicating that leukotrienes mediate 5-HT-induced PE via CysLT receptors. In contrast, antagonists selective for LTB(4) receptors (BLT(1) and BLT(2) receptors) failed to reduce 5-HT-induced PE.
These results demonstrate that leukotrienes, specifically cysteinyl-leukotrienes contribute to synovial plasma extravasation and suggest that leukotrienes act downstream of 5-HT in the inflammatory cascade.
本研究旨在探究由5-脂氧合酶（5-LO）合成并通过白三烯（LT）受体起作用的白三烯是否参与5-羟色胺（5-HT）诱导的膝关节血浆外渗（PE）。
对麻醉状态下大鼠的膝关节灌注5-HT，并通过分光光度法测量滑膜血管伊文思蓝染料渗漏情况。研究了一系列5-LO抑制剂和LT受体拮抗剂抑制5-HT诱导的滑膜PE的能力。
5-LO抑制剂（去甲二氢愈创木酸和REV 5901）显著减弱了5-HT诱导的血浆外渗。MK 571、LY 171883、BAY u9773（半胱氨酰白三烯受体拮抗剂）和REV 5901（一种半胱氨酰白三烯受体拮抗剂和5-LO抑制剂）在抑制5-HT诱导的PE方面同样有效，表明白三烯通过半胱氨酰白三烯受体介导5-HT诱导的PE。相比之下，对白三烯B4受体（BLT1和BLT2受体）具有选择性的拮抗剂未能减少5-HT诱导的PE。
这些结果表明，白三烯，特别是半胱氨酰白三烯参与滑膜血浆外渗，并提示白三烯在炎症级联反应中作用于5-HT的下游。
