Langer J C, Sohal S S, Blennerhassett P
Intestinal Disease Research Unit, McMaster University, Hamilton, Ontario.
J Pediatr Surg. 1995 Apr;30(4):568-72. doi: 10.1016/0022-3468(95)90133-7.
Changes in mucosal permeability may be important in the etiology of necrotizing enterocolitis. The authors have previously shown that subclinical ischemia-reperfusion injury results in increased permeability in the rat intestine, and have partially characterized this phenomenon. In the present study the authors attempt to determine the mechanism by which these changes occur. Six-week-old rats underwent 10-minute superior mesenteric artery occlusion (SMAO) or sham, and mucosal permeability to 51CrEDTA was measured after 30 minutes. Rats were pretreated with saline, inhibitors of oxygen free radicals (superoxide dismutase+catalase, vitamin E, allopurinol, alpha-phenyl-N-tert butyl-nitrone), inhibitors of eicosanoids (indomethacin, quinacrine, diethylcarbamazine, 13-azaprostanoic acid), the putative cytoprotective agent prostaglandin E2, or the inhibitor of neutrophil free radical production fructose 1-6 diphosphate. None of the agents significantly attenuated the increase in mucosal permeability caused by SMAO, although indomethacin and prostaglandin E2 significantly exacerbated the permeability changes. To further explore the role of neutrophils, tissue myeloperoxidase was measured 30 minutes after SMAO. There was no significant difference in myeloperoxidase levels between sham and SMAO animals. These data suggest that the early increase in mucosal permeability after subclinical ischemia-reperfusion injury is not mediated by oxygen free radicals, eicosanoids, or neutrophils. The deleterious effect of indomethacin and prostaglandin E2 suggests a possible protective role for the cyclooxygenase system, but further studies are necessary to elucidate this possibility.
黏膜通透性的改变可能在坏死性小肠结肠炎的病因学中起重要作用。作者先前已表明，亚临床缺血-再灌注损伤会导致大鼠肠道通透性增加，并已对这一现象进行了部分特征描述。在本研究中，作者试图确定这些变化发生的机制。六周龄大鼠接受10分钟的肠系膜上动脉闭塞（SMAO）或假手术，30分钟后测量黏膜对51CrEDTA的通透性。大鼠分别用生理盐水、氧自由基抑制剂（超氧化物歧化酶+过氧化氢酶、维生素E、别嘌呤醇、α-苯基-N-叔丁基硝酮）、类花生酸抑制剂（吲哚美辛、奎纳克林、乙胺嗪、13-氮杂前列腺素酸）、假定的细胞保护剂前列腺素E2或中性粒细胞自由基产生抑制剂1,6-二磷酸果糖进行预处理。尽管吲哚美辛和前列腺素E2显著加剧了通透性变化，但这些药物均未显著减轻SMAO引起的黏膜通透性增加。为了进一步探讨中性粒细胞的作用，在SMAO后30分钟测量组织髓过氧化物酶。假手术组和SMAO组动物的髓过氧化物酶水平无显著差异。这些数据表明，亚临床缺血-再灌注损伤后早期黏膜通透性增加不是由氧自由基、类花生酸或中性粒细胞介导的。吲哚美辛和前列腺素E2的有害作用提示环氧化酶系统可能具有保护作用，但需要进一步研究以阐明这种可能性。
