Bertrán X, Mañé J, Fernández-Bañares F, Castellá E, Bartolí R, Ojanguren I, Esteve M, Gassull M A
Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Gut. 1996 Jun;38(6):899-904. doi: 10.1136/gut.38.6.899.
5-Lipoxygenase products play a part in inflammatory response.
The effect of intracolonic administration of zileuton (a 5-lipoxygenase inhibitor) on colonic damage and eicosanoid local release was assessed in a rat model of colitis.
Ninety rats with trinitrobenzenesulphonic acid induced colitis were randomised to receive placebo, 5-aminosalicylic acid (50 mg/kg), or zileuton (50 mg/kg) intracolonically for four weeks. Local eicosanoid release was monitored by intracolonic dialysis throughout the study. The colon was removed for macroscopic and histological assessment at weeks 1, 2, and 4 after colitis induction in 10 rats of each group.
Zileuton significantly reduced macroscopic damage score after four weeks of treatment in comparison with the other two groups (p = 0.034). In addition, zileuton administration significantly increased the intracolonic release of both thromboxane B2 at week 1 (p = 0.05) and prostaglandin E2 at weeks 2 and 4 (p < 0.05). Zileuton and 5-aminosalicylic acid decreased leukotriene B4 release by 90% at day 3.
Intracolonic zileuton, compared with 5-aminosalicylic acid and placebo, seems to improve the course of the disease in a model of chronic colitis. This effect may be related to an increased and maintained production of prostaglandin E2 together with inhibition of leukotriene B4 synthesis.
5-脂氧合酶产物参与炎症反应。
在大鼠结肠炎模型中评估结肠内给予齐留通（一种5-脂氧合酶抑制剂）对结肠损伤和类花生酸局部释放的影响。
将90只经三硝基苯磺酸诱导的结肠炎大鼠随机分为三组，分别结肠内给予安慰剂、5-氨基水杨酸（50mg/kg）或齐留通（50mg/kg），持续四周。在整个研究过程中，通过结肠内透析监测局部类花生酸的释放。每组10只大鼠在结肠炎诱导后第1、2和4周处死，取出结肠进行大体和组织学评估。
与其他两组相比，治疗四周后齐留通显著降低了大体损伤评分（p = 0.034）。此外，给予齐留通显著增加了第1周血栓素B2（p = 0.05）以及第2和4周前列腺素E2（p < 0.05）的结肠内释放。在第3天，齐留通和5-氨基水杨酸使白三烯B4释放减少了90%。
与5-氨基水杨酸和安慰剂相比，结肠内给予齐留通似乎可改善慢性结肠炎模型中的病程。这种作用可能与前列腺素E2生成增加并维持以及白三烯B4合成受抑制有关。
