Improvement and assessment of a neonatal murine model of necrotizing enterocolitis

Objective To improve and evaluate the model of necrotizing enterocolitis (NEC) in C57BL/6 neonatal mice so as to provide experimental rationales for further pathogenic studies of NEC. Methods Two-day-old C57BL/6 neonatal mice were randomly divided by a ratio of 3: 1 into NEC (n=36) and control (n=11) groups. The NEC group was stressed by hypoxia and hypothermia plus an intraperitoneal injection of lipopolysaccharide (LPS) while the control group had no stress factors. The inter-group differences of clinical status, macroscopic gut and histology were compared. Histological scores of 3 or 4 were considered to have developed NEC. Results NEC was present in 71% of NEC group. Control mice showed no evidence of NEC. Clinical sickness score was higher in NEC group (median=7; range=3-12) than controls (median=0; range=0-1; P<0.01). There were decreases in proliferative activity and cell migration and enterocyte apoptosis intensified. The expressions of ICAM, CXCL-1, CXCL-2 and Lgr5 were significantly different from those in controls. Conclusions The study has established a stable and reliable 2-day-old C57BL/6 murine model of NEC through hypoxia, hypothermia and LPS. And it may be used for further studies of NEC. Key words: Enterocolitis, necrotizing; Mice; Models, animal