Department of Surgery, University of Alberta, Edmonton, Alta., Canada.
Neonatology. 2009;96(3):162-70. doi: 10.1159/000210089. Epub 2009 Mar 31.
Neonatal asphyxia may lead to the development of ischemia-reperfusion induced intestinal injury, which is related to oxygen-derived free radical production. N-Acetylcysteine (NAC) is a thiol-containing antioxidant which increases intracellular stores of glutathione.
Using a swine model of neonatal hypoxia-reoxygenation, we examined whether administration of NAC after resuscitation improved intestinal perfusion and reduced intestinal damage.
Twenty-four piglets (1-4 days old, 1.4-2.2 kg) were anesthetized and acutely instrumented for continuous monitoring of superior mesenteric arterial flow and oxygen delivery. Alveolar hypoxia was induced for 2 h, followed by resuscitation with 100% oxygen for 1 h and 21% oxygen for 3 h. Animals were randomized to sham-operated, hypoxic control and NAC treatment (150 mg/kg i.v. at 0 or 10 min of reoxygenation followed by infusion 100 mg/kg/h) groups. During hypoxia-reoxygenation, intestinal tissue glutathione content, caspase-3 activity and reoxygenation injury were examined.
After 2 h of hypoxia, piglets were acidotic and hypotensive, with significantly depressed blood flow and oxygen delivery to the small intestine. Upon reoxygenation, hemodynamics recovered as did oxygen supply to the small intestine. After 4 h of reoxygenation, the NAC treatment improved mesenteric flow and oxygen delivery. Despite reducing the increase in caspase-3 activities after hypoxia-reoxygenation by NAC treatment, no significant differences in the glutathione content and histological grading of ileal injury were found among the experimental groups.
In newborn piglets with hypoxia-reoxygenation, NAC may improve mesenteric blood flow and oxygen delivery without significant effect on tissue glutathione content. The protective role of NAC in the reoxygenated intestine after severe hypoxia warrants further investigation.
新生儿窒息可能导致缺血再灌注诱导的肠损伤，这与氧自由基的产生有关。N-乙酰半胱氨酸（NAC）是一种含巯基的抗氧化剂，可增加细胞内谷胱甘肽的储存。
我们使用新生猪缺氧-再复氧模型，研究了复苏后给予 NAC 是否改善了肠道灌注并减少了肠道损伤。
24 头小猪（1-4 天龄，1.4-2.2 公斤）接受麻醉并进行急性仪器监测，以连续监测肠系膜上动脉流量和氧输送。诱导肺泡缺氧 2 小时，然后用 100%氧气复苏 1 小时，用 21%氧气复苏 3 小时。动物随机分为假手术、缺氧对照组和 NAC 治疗组（再复氧 0 或 10 分钟时给予 150mg/kg 静脉注射，然后以 100mg/kg/h 的速度输注）。在缺氧-再复氧过程中，检查肠道组织谷胱甘肽含量、半胱天冬酶-3 活性和再复氧损伤。
缺氧 2 小时后，小猪出现酸中毒和低血压，小肠血流和氧输送显著减少。再复氧时，血流动力学恢复，小肠氧供也恢复。再复氧 4 小时后，NAC 治疗改善了肠系膜血流和氧输送。尽管 NAC 治疗降低了缺氧-再复氧后半胱天冬酶-3 活性的增加，但在实验组之间，谷胱甘肽含量和回肠损伤的组织学分级没有发现显著差异。
在新生猪缺氧-再复氧模型中，NAC 可能改善肠系膜血流和氧输送，而对组织谷胱甘肽含量无明显影响。NAC 在严重缺氧后再复氧肠中的保护作用值得进一步研究。
