Luo C C, Chen H M, Chiu C H, Lin J N, Chen J C
Department of Pediatric Surgery and Pediatrics, Chang Gung Children's Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Biol Neonate. 2001 Jul;80(1):60-3. doi: 10.1159/000047121.
Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis in premature infants. Previous studies suggested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuries from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an increase in intestinal permeability in rats following IRI. Sprague-Dawley rats weighing 200-300 g were divided into 4 groups: (1) untreated group (normal control); (2) ischemia-reperfusion group; (3) early N(G)-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO production, treatment group, and (4) late L-NAME treatment group. Transient IRI was induced by 30-min occlusion, followed by reperfusion of the isolated ileal loop. The L-NAME was administered 15 min before and after mesenteric ischemia as a 25-mg/kg bolus. Fluorescein isothiocyanate-dextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was no significant increase in the portal vein FITC-D level among normal controls, ischemia-reperfusion group and late L-NAME-treated group, but there was an approximately 6-fold increase in the early L-NAME treatment group. The pathological features of the intestine following IRI include denudation of the villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results suggest that endogenous NO may play a role in the protecting intestinal integrity after IRI.
亚临床肠缺血再灌注损伤（IRI）会导致黏膜通透性增加，可能是早产儿坏死性小肠结肠炎发病机制中的早期事件。先前的研究表明，一氧化氮（NO）的持续内源性生成维持肠道黏膜完整性，从而保护肠道免受血源性毒素和组织破坏介质的损伤。本研究旨在评估抑制NO生成是否会导致IRI后大鼠肠通透性增加。将体重200 - 300 g的Sprague-Dawley大鼠分为4组：（1）未处理组（正常对照）；（2）缺血再灌注组；（3）早期N（G）-硝基-L-精氨酸甲酯（L-NAME）处理组，L-NAME是一种NO生成的特异性抑制剂；（4）晚期L-NAME处理组。通过对分离的回肠袢进行30分钟的阻断，随后再灌注诱导短暂性IRI。在肠系膜缺血前后15分钟给予L-NAME，剂量为25 mg/kg推注。用异硫氰酸荧光素-葡聚糖（FITC-D）定量评估肠道黏膜通透性的变化。正常对照组、缺血再灌注组和晚期L-NAME处理组门静脉FITC-D水平无显著升高，但早期L-NAME处理组升高了约6倍。IRI后肠道的病理特征包括绒毛上皮剥脱和绒毛高度降低，伴有固有层明显的炎性细胞浸润。这些结果表明内源性NO可能在IRI后保护肠道完整性中发挥作用。
