Tian Runlan, Liu Shirley Xl, Williams Cara, Soltau Thomas D, Dimmitt Reed, Zheng Xiaotian, De Plaen Isabelle G
Int J Clin Exp Med. 2010 Sep 21;3(4):293-302.
Necrotizingenterocolitis (NEC) is a major health concern for premature infants and its patho-genesis remains poorly understood. The current mouse NEC model has not well been characterized.
In this study, we develop a simple mouse model of NEC and determine the role of several factors modulating human NEC (i.e., breast milk, birth weight, cesarean section and bacteria) on intestinal injury.
In a first experiment, pups born naturally and dam fed for <12 hours were gavaged with adult commensal bacteria or E. Fecalis, and exposed to hypoxia-cold stress-formula feeding, and compared with controls without bacteria inoculation. 72-hour mortality was recorded, and small intestines were examined histologically. In a second experiment, we compared the incidence of NEC in mice dam fed for <12 hours to those dam fed for 12 to 24 hours or delivered by cesarean section prior to being submitted to the NEC protocol.
In pups inoculated with 10(7) CFU of a standardized preparation of adult commensal bacteria or 10(5) CFU of E. Fecalis, the incidence of severe NEC (>grade 2) was 70% and 37% respectively vs 6% in the controls (no bacteria)(p<0.05). In pups dam fed for 12 to 24 hours, NEC incidence was 44(±12)% lower vs those dam fed less than 12 hours (p<0.05). We did not find any difference in the NEC incidence between naturally-born pups dam fed for less than 12 hours and these born by cesarean section. The incidence of severe NEC was higher in pups with low birth weight.
we have simplified and characterized a neonatal mouse NEC model that shares several risk factors with human NEC. Now that transgenic mice are available, this model will be useful to study the role played by specific proteins in vivo in NEC development.
坏死性小肠结肠炎（NEC）是早产儿的主要健康问题，其发病机制仍知之甚少。目前的小鼠NEC模型尚未得到充分表征。
在本研究中，我们建立了一种简单的小鼠NEC模型，并确定了几种调节人类NEC的因素（即母乳、出生体重、剖宫产和细菌）对肠道损伤的作用。
在第一个实验中，对自然出生且母鼠喂养不足12小时的幼崽灌胃成年共生菌或粪肠球菌，使其暴露于缺氧-冷应激-配方奶喂养环境中，并与未接种细菌的对照组进行比较。记录72小时死亡率，并对小肠进行组织学检查。在第二个实验中，我们比较了母鼠喂养不足12小时的小鼠与母鼠喂养12至24小时或在接受NEC方案之前剖宫产出生的小鼠的NEC发病率。
接种10⁷CFU标准化成年共生菌制剂或10⁵CFU粪肠球菌的幼崽中，严重NEC（>2级）的发病率分别为70%和37%，而对照组（未接种细菌）为6%（p<0.05）。母鼠喂养12至24小时的幼崽，NEC发病率比母鼠喂养不足12小时的幼崽低44（±12）%（p<0.05）。我们发现自然出生且母鼠喂养不足12小时的幼崽与剖宫产出生的幼崽之间的NEC发病率没有差异。低出生体重幼崽的严重NEC发病率更高。
我们简化并表征了一种与人类NEC有若干共同危险因素的新生小鼠NEC模型。鉴于已有转基因小鼠，该模型将有助于研究特定蛋白质在NEC体内发育中的作用。
