Zani Augusto, Eaton Simon, Leon Francesco Fascetti, Malerba Alberto, Hall Nigel J, De Coppi Paolo, Smith Virpi V, Pierro Agostino
Department of Paediatric Surgery, Institute of Child Health, WC1N 1EH London, UK.
J Pediatr Surg. 2008 Feb;43(2):308-14. doi: 10.1016/j.jpedsurg.2007.10.022.
BACKGROUND/PURPOSE: Selective mesenteric ischemia may result from activation of the renin-angiotensin system during periods of shock and is implicated in the pathogenesis of neonatal necrotizing enterocolitis (NEC). We investigated the effectiveness of captopril, an angiotensin-converting enzyme inhibitor, in reducing the severity of bowel damage in a neonatal rat model of NEC.
Necrotizing enterocolitis was induced by a combination of gavage feeding of hypertonic formula, hypoxia, and oral lipopolysaccharide (LPS). Rats were randomly divided into 3 groups: group A, control (breast fed; n = 20); group B, NEC (gavage/hypoxia/LPS; n = 31); group C, NEC with captopril 20 mg/kg per dose with the formula for 4 days (gavage/hypoxia/LPS/captopril; n = 35). Pups were killed after 4 days. Incidence of NEC was evaluated microscopically.
Severity of bowel damage was higher in the NEC group compared to controls and was reduced by administration of captopril. Dilatation of the intestinal vasculature was observed in the captopril group. There were no cases of NEC in the controls; the incidence increased to 55% in NEC group and reduced to 29% by captopril.
In this model of neonatal NEC, captopril supplementation of formula reduces the severity of intestinal damage and the incidence of NEC, presumably by affecting mesenteric blood flow.
背景/目的：选择性肠系膜缺血可能源于休克期间肾素-血管紧张素系统的激活，并与新生儿坏死性小肠结肠炎（NEC）的发病机制有关。我们研究了血管紧张素转换酶抑制剂卡托普利在减轻NEC新生大鼠模型肠道损伤严重程度方面的有效性。
通过胃管喂养高渗配方奶、缺氧和口服脂多糖（LPS）联合诱导坏死性小肠结肠炎。大鼠随机分为3组：A组，对照组（母乳喂养；n = 20）；B组，NEC组（胃管喂养/缺氧/LPS；n = 31）；C组，NEC + 卡托普利组，每剂20 mg/kg，与配方奶一起给予4天（胃管喂养/缺氧/LPS/卡托普利；n = 35）。4天后处死幼崽。通过显微镜评估NEC的发生率。
与对照组相比，NEC组肠道损伤严重程度更高，而给予卡托普利可减轻损伤。在卡托普利组观察到肠道血管扩张。对照组无NEC病例；NEC组发生率增至55%，卡托普利治疗后降至29%。
在这个新生大鼠NEC模型中，配方奶中添加卡托普利可减轻肠道损伤严重程度并降低NEC发生率，可能是通过影响肠系膜血流实现的。
