The viral dsRNA analogue poly (I:C) induces necrotizing enterocolitis in neonatal mice
The viral dsRNA analogue poly (I:C) induces necrotizing enterocolitis in neonatal mice
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DOI：
10.1038/pr.2015.261
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发表时间：
2016-04-01
影响因子：
3.6
通讯作者：
Lacher, Martin
中科院分区：
文献类型：
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作者：
Ginzel, Marco;Yu, Yi;Lacher, Martin
背景：坏死性小肠结肠炎（NEC）是一种危及早产儿生命的胃肠道疾病，死亡率高，发病率高，发病机制不确定。最近的研究主要集中在腔内细菌和脂多糖（LPS）的作用上。然而，最近假设病毒制剂在NEC发病机制中的另一个作用。我们评估了多肌苷：多胞苷酸（pIC）模拟病毒dsRNA在新生小鼠NEC发展中的作用。方法：4龄C57BL/6J幼犬每日2次进行窒息和低温应激。动物分别饲喂纯配方饲料（FO）、含LPS配方饲料或pIC配方饲料。72h后，对小鼠实施安乐死，取肠，评估NEC的严重程度。结果：母乳喂养小鼠未见NEC。在喂食鱼油的小鼠中观察到非常轻微的nec样病变。与鱼油相比，在配方中添加LPS或pIC导致肠道组织损伤和炎症增加。结论：我们的研究表明，即使在缺乏LPS的情况下，病毒因子也能诱导新生小鼠NEC。此外，我们提出了一种新的小鼠模型- pic诱导NEC，可用于进一步了解这种疾病的发病机制。
Background: 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.Methods: 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.Results: 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.Conclusion: 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.