El-Medany Azza, Mahgoub Afaf, Mustafa Ali, Arafa Maha, Morsi Mahmoud
Department of Pharmacology, College of Medicine, King Saud University, Riyadh 11461, P.O. Box 22452, Saudi Arabia.
Eur J Pharmacol. 2005 Jan 10;507(1-3):291-9. doi: 10.1016/j.ejphar.2004.11.036. Epub 2004 Dec 15.
Several mediators may be involved in the pathogenesis of inflammatory bowel disease, as well as in experimental colitis. The present work was conducted to investigate the effects of the two selective cyclooxygenase-2 inhibitors, celecoxib and rofecoxib, on experimentally induced colitis in rats. Rectal instillation of acetic acid was used to induce the colitis. Acetic acid treatment caused haemorrhagic diarrhoea and weight loss in rats. Celecoxib (5 mg/kg) or rofecoxib (2.5 mg/kg), when given twice daily by the oral route, reduced the degree of haemorrhagic diarrhoea and the weight loss produced. In addition, they produced a significant reduction in the degree of colonic injury, the rise in myeloperoxidase (MPO) levels, total nitric oxide synthetase (NOS) activity, platelet-activating factor (PAF), histamine levels and prostaglandin E2 levels. In contrast, there was a significant increase in the levels of reduced glutathione (GSH). Thus, the findings of the present study provide evidence that selective cyclooxygenase-2 inhibitors may be beneficial in patients with inflammatory bowel disease.
几种介质可能参与炎症性肠病以及实验性结肠炎的发病机制。开展本研究以调查两种选择性环氧化酶-2抑制剂塞来昔布和罗非昔布对大鼠实验性结肠炎的影响。采用直肠灌注乙酸诱导结肠炎。乙酸处理导致大鼠出现出血性腹泻和体重减轻。塞来昔布(5毫克/千克)或罗非昔布(2.5毫克/千克)每日经口给药两次,可减轻出血性腹泻的程度和所导致的体重减轻。此外,它们还能显著减轻结肠损伤程度、降低髓过氧化物酶(MPO)水平、总一氧化氮合酶(NOS)活性、血小板活化因子(PAF)、组胺水平和前列腺素E2水平。相比之下,还原型谷胱甘肽(GSH)水平显著升高。因此,本研究结果提供了证据表明选择性环氧化酶-2抑制剂可能对炎症性肠病患者有益。