Xu Lingqi,Ma Shurong,Chen Lulu,et al.Improvements and evaluations of animal models of neonatal necrotizing enterocolitis[J].Journal of Clinical Pediatric Surgery,,22():569-575.[doi:10.3760/cma.j.cn101785-202202036-014]
Improvements and evaluations of animal models of neonatal necrotizing enterocolitis
- Keywords:
- Enterocolitis; Necrotizing; Models; Animal; Feasibility Studies
- Abstract:
- Objective The construction of animal models of neonatal necrotizing enterocolitis (NEC) is still not uniform, and animal modeling approaches that are more relevant to the actual clinical situation of NEC childern should be clarified.Methods Fifly-four newborn mice were randomized into five groups of control (Ctrl), hypoxia plus artificial feeding (HF), hypoxia plus artificial feeding plus cold stimulation (Cold), hypoxia plus artificial feeding plus lipopolysaccharide (LPS) and hypoxia plus artificial feeding plus intestinal bacteria in NEC (Bac).After successful modeling, intestinal pathology, NEC-related intestinal epithelial barrier proteins (β-catenin & Occludin), intestinal epithelial cell death (CC3, RIPK1 & PARP1) and pro-inflammatory cytokines (IL-6, TNF-α & MCP1) were evaluated.Results Nadler score ≥ 2 according to intestinal histology was considered as NEC-like intestinal injury. In this study, the intestinal histopathology of the three NEC-modeled groups met the criteria for NEC-like intestinal injury, except for the Ctrl and HF groups. Compared with the NEC modeling groups HF (30%), Cold (83.3%) and LPS (81.8%), the Bac group had the highest modeling success rate (100%), and the mental status, bloating and diarrhea, and mobility of the mice in the Bac group during the modeling period were more consistent with clinical NEC. Meanwhile, the expression of intestinal barrier proteins β-catenin and Occludin was decreased in the Bac group mice, and the difference was statistically significant compared with the Ctrl group (P<0.05). the expression of intestinal epithelial cell death marker molecules RIPK1 and PARP1 was upregulated in the LPS and Bac groups, and the expression levels of inflammatory factors IL-6, TNF-α and MCP1 were increased compared with the Ctrl group, with statistically significant differences (P<0.05). Conclusion This study has successfully established four NEC animal models and verified a more appropriate animal modeling method of clinical NEC, namely "hypoxia plus artificial feeding plus NEC intestinal bacteria".Such a modeling method has a high success rate.And intestinal histopathological injury, intestinal barrier protein expression and systemic inflammatory response mimic closely the clinical characteristics of NEC.
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Memo
收稿日期:2022-02-07。
基金项目:江苏省卫生健康委医学科研项目（H2019002）
通讯作者:汪健,Email:wj196312@vip.163.com