Andreadou Ioanna, Poussios Dimitrios, Papalois Apostolos, Gavalakis Nikolaos, Aroni Kyriaki, Gazouli Maria, Gorgoulis Vassilis G, Fotiadis Constantinos
3rd Department of Surgery, Sotiria Hospital, Athens, Greece.
In Vivo. 2003 Sep-Oct;17(5):463-8.
Although it has been demonstrated that lazaroids can protect various organs from ischemia reperfusion injury, results obtained in the small intestine have been conflicting. On the other hand, it is not known whether inhibition of lipid peroxidation prevents intestinal ishemia-reperfusion injury. We investigated whether the administration of the aminolazaroid U-74389G had 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, U-74389G was administered intravenously and the clamp was removed to allow reperfusion. At 60 min after reperfusion animals were sacrificed and a 10-cm section of terminal ileum was resected. Its efficacy was evaluated by histopathological assessment, measurement of polymorphonuclear leukocytes and the extent of lipid peroxidation by measuring the small intestine tissue malondialdehyde. After 1 h of reperfusion, mucosal damage in both U-74389G-treated rats and control group rats was similar. However, the number of polymorphonuclear leukocytes in the intestinal mucosa was lower in the U-74389G group. Of particular interest was that U-74389G resulted in a statistically significant reduction in the concentration of small intestine tissue malondialdehyde, compared to the controls. When administered in an imitated clinical setting, U-74389G did not prevent intestinal ischemia reperfusion injury, however it protected the rat small intestine from oxidative damage by inhibiting lipid peroxidation.
尽管已证明拉扎oids可保护各种器官免受缺血再灌注损伤，但在小肠中获得的结果却相互矛盾。另一方面，脂质过氧化的抑制是否能预防肠道缺血再灌注损伤尚不清楚。我们在一项随机双盲试验中研究了氨基拉扎oid U-74389G的给药对短暂性肠系膜缺血后肠黏膜修复过程是否具有有益作用。将六组大鼠制成肠系膜上动脉闭塞导致的60分钟肠道缺血模型。在缺血结束时，静脉注射U-74389G，然后松开血管夹以实现再灌注。再灌注60分钟后处死动物，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通过测量小肠组织丙二醛来评估脂质过氧化程度，以此评价其疗效。再灌注1小时后，U-74389G治疗组大鼠和对照组大鼠的黏膜损伤相似。然而，U-74389G组肠黏膜中的多形核白细胞数量较少。特别值得注意的是，与对照组相比，U-74389G使小肠组织丙二醛浓度在统计学上显著降低。在模拟临床环境中给药时，U-74389G不能预防肠道缺血再灌注损伤，然而它通过抑制脂质过氧化保护大鼠小肠免受氧化损伤。
