Abstract:Objective To investigate the mechanism of LR12 peptide on intestinal damage in necrotic enterocolitis (NEC) in neonatal mice. Methods A total of 18 SPF C57BL/6 mice (6 females, 12 males), 8 weeks, weight 16-23 g. Sixty pups born after the female rat pregnancy, they were divided into control group, model group, LR12-scr group and LR12 group according to random number table method, with 15 pups in each group. The control group did not take any operation, and the other three groups established NEC model. After successful model construction, lR12-scr group was intraperitoneally injected with 5 mg/kg LR12 scramble, LR12 group was intraperitoneally injected with 5 mg/kg LR12 peptide, control group and model group were intraperitoneally injected with equal dose of solvent once a day for consecutive three days. The indexes of young rats in each group were compared. Results Compared with the control group, clinical symptom score, intestinal histopathological score, the intestinal permeability, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 and the protein expressions levels of triggering receptor expressed on myeloid cells-1, TLR-4, MyD88, and NF-κB p65 were increased in the model group, while weight and the expression levels of IκBα were dereased, the differences were statistically significant (P < 0.05). Compared with the model group, clinical symptom score, intestinal histopathological score, the intestinal permeability, the levels of TNF-α, IL-1β, and IL-6 and the protein expression levels of TREM1, TLR-4, MyD88, and NF-κB p65 were decreased in the LR12 group, while weight and the expression level of IκBα were increased, the differences were statistically significant (P < 0.05). There were no statistical signficances in the above indicators between LR12-scr group and model group (P > 0.05). Conclusion LR12 peptide has improved intestinal permeability, reduced intestinal inflammation and injury in NEC neonatal mice, and the mechanism may be related to inhibiting TLR-4/NF-κB signaling pathway activation.