Poussios Dimitrios, Andreadou Ioanna, Papalois Apostolos, Rekka Eleni, Gavalakis Nikolaos, Aroni Kyriaki, Kourounakis Panos N, Fotiadis Constantinos, Sechas Michael N
3rd Department of Surgery, "Sotiria" Hospital, University of Athens School of Medicine, Athens, Greece.
Eur J Pharmacol. 2003 Apr 4;465(3):275-80. doi: 10.1016/s0014-2999(03)01488-2.
Reactive oxygen species play an important role in the basic pathophysiology of ischemia-reperfusion injury. We investigated whether the administration of a novel non-steroidal anti-inflammatory compound with antioxidant properties, the compound [5-(2-amino-ethylamino)-1-phenyl-2-pentanone] (compound IA), has a beneficial effect on the repair process of the intestinal mucosa after transient mesenteric ischemia in a randomized blind trial. Six groups of rats were subjected to a model of 60 min of intestinal ischemia that was produced by occluding the superior mesenteric artery. At the end of ischemia, compound IA was administered intravenously and the clamp was removed allowing reperfusion. At 60 min after reperfusion, animals were sacrificed and a 10 cm section of terminal ileum was resected. The outcome was evaluated by histopathologic assessment, measurement of polymorphonuclear leukocytes and the extent of lipid peroxidation measuring the small intestine tissue malondialdehyde. After 1 h of reperfusion, the mucosal damage was less in IA-treated rats compared with the control group. Moreover, the number of polymorphonuclear leukocytes in intestinal mucosa was significantly lower in IA group. Compound IA resulted in a statistically significant reduction of the concentration of small intestine tissue malondialdehyde, compared to those of controls. Administration of compound IA decreased the mucosal damage in rats that were subjected to 60 min of ischemia followed by 60 min of reperfusion. The mechanism of compound IA action is considered to be mediated via its potent antioxidant, free radical scavenging activities and inhibition of polymorphonuclear leukocytes infiltration.
活性氧在缺血再灌注损伤的基本病理生理学中起着重要作用。我们在一项随机盲法试验中研究了一种具有抗氧化特性的新型非甾体抗炎化合物5-(2-氨基乙氨基)-1-苯基-2-戊酮的给药是否对短暂性肠系膜缺血后肠黏膜的修复过程具有有益作用。将六组大鼠制成肠系膜上动脉闭塞导致的60分钟肠缺血模型。缺血结束时,静脉注射化合物IA,然后松开血管夹进行再灌注。再灌注60分钟后,处死动物并切除10厘米长的回肠末端。通过组织病理学评估、多形核白细胞计数以及测量小肠组织丙二醛评估脂质过氧化程度来评价结果。再灌注1小时后,与对照组相比,接受IA治疗的大鼠黏膜损伤较轻。此外,IA组肠黏膜中的多形核白细胞数量显著减少。与对照组相比,化合物IA使小肠组织丙二醛浓度在统计学上显著降低。给予化合物IA可减轻经历60分钟缺血和60分钟再灌注的大鼠的黏膜损伤。化合物IA的作用机制被认为是通过其强大的抗氧化、自由基清除活性以及抑制多形核白细胞浸润来介导的。