Ginzel Marco, Yu Yi, Klemann Christian, Feng Xiaoyan, von Wasielewski Reinhard, Park Joon-Keun, Hornef Mathias W, Torow Natalia, Vieten Gertrud, Ure Benno M, Kuebler Joachim F, Lacher Martin
Center of Pediatric Surgery, Hannover Medical School, Hannover, Germany.
Department of Pediatrics, Hannover Medical School, Hannover, Germany.
Pediatr Res. 2016 Apr;79(4):596-602. doi: 10.1038/pr.2015.261. Epub 2015 Dec 17.
Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disease in premature infants with high mortality and morbidity with uncertain pathogenesis. Recent research focused on the role of intraluminal bacteria and lipopolysaccharide (LPS). However, an additional role of viral agents in the pathogenesis of NEC has recently been postulated. We assessed the role of polyinosinic:polycytidylic acid (pIC) mimicking viral dsRNA in contributing to the development of NEC in neonatal mice.
Four-d-old C57BL/6J pups were stressed by asphyxia and hypothermia twice daily. Animals were either fed by formula only (FO), formula containing LPS or pIC. After 72 h, mice were euthanized, intestines harvested, and the severity of NEC was assessed.
Breastfed mice showed no evidence of NEC. Very mild NEC-like lesions were observed in mice fed by FO. Supplementation of LPS or pIC to the formula led to increased intestinal tissue damage and inflammation compared with FO in a similar manner.
Our study demonstrates the ability of viral factors to induce NEC in neonatal mice even in the absence of LPS. Furthermore, we present a new mouse model of pIC-induced NEC which may be used to obtain further mechanistic insights in the pathogenesis of this disease.
坏死性小肠结肠炎(NEC)是一种危及生命的胃肠道疾病,在早产儿中具有高死亡率和发病率,其发病机制尚不确定。最近的研究集中在肠腔内细菌和脂多糖(LPS)的作用上。然而,最近有人推测病毒因子在NEC发病机制中也起作用。我们评估了模拟病毒双链RNA的聚肌苷酸:聚胞苷酸(pIC)在新生小鼠NEC发生发展中的作用。
对4日龄的C57BL/6J幼崽每天进行两次窒息和低温应激。动物分别仅喂食配方奶(FO)、含LPS的配方奶或含pIC的配方奶。72小时后,对小鼠实施安乐死,取出肠道,评估NEC的严重程度。
母乳喂养的小鼠未出现NEC迹象。喂食FO的小鼠观察到非常轻微的类NEC病变。与FO相比,在配方奶中添加LPS或pIC会以类似的方式导致肠道组织损伤和炎症增加。
我们的研究表明,即使在没有LPS的情况下,病毒因子也能够在新生小鼠中诱发NEC。此外,我们提出了一种新的pIC诱导的NEC小鼠模型,可用于进一步深入了解该疾病的发病机制。