Extracellular Signal-regulated Kinases Mediate The Protective Effect Of Intestinal Trefoil Factor On Neonatal Rats With Necrotizing Enterocolitis

Objective: Intestinal trefoil factor (ITF) is closely related with gastrointestinal epithelial cells injury repairment. Studing the effects of ITF on necrotizing enterocolitis (NEC) would be helpful to the treatment of NEC.This research investigated the effect of ITF on intestinal histopathological changes, productions of prostaglandin E2 (PGE2 )and thromboxane B2 (TXB2) in neonatal rats with necrotizing enterocolitis (NEC) to explore whether ITF has therapeutic effect in NEC.and if the extracellular signal- regulated kinases (ERK1/2) pathway activatied in the protective effect of intestinal trefoil factor (ITF) on neonatal rats with NEC.Methods: Forty One-day old Wistar rats were randomly divided into 5 groups (8 rats each group). The group A was the normal control group. Rats in the Group B, C, D and E were made NEC model by hypoxia and reoxygenation for consecutive 3 days. Group D and E were treated with 0.5 mL ITF (0.5 mg) intraperitoneal injection or 0.2 mL ITF (0.2 mg) subcutaneous injection once respectively after damage, while Group B and C were treated with normal saline intraperitoneally or subcutaneously respectively. NEC model were made as follow: CO₂ was added to the hypoxia chamber, when the concentration reached 100%, neonatal rats were put into hypoxia chamber for 5 minutes, then were taken out, and O₂ was added quickly till O₂ concentration reached 100%, the post-hypoxia rats were put into it for another 5 minutes. This process was carried out for a successive 3 days. On the 4^th day all the rats are sacrificed, and intestinal tissue were obtained to exam the histological changes, PGE₂ and TXB2 productions and western blotting for the change of ERK1/2 phosphorylation.Results: Intestinal histopathology of rats in the Group A was normal, and the scores were 0. As compared with the corresponding NEC group (Group B and C), histopathological injury of NEC was remarkably relieved after ITF treatment (Group D and E) (P < 0.01). Scores of rats in the Group B and C were 1-4, while those of Group D and E were 0-2. PGE2 and TXB₂ contents were significantly increased in Group B and C, while dramatic decreased after ITF treatment (in Group D and E). No significant difference was observed between Group D, E and A. the Phosphorylation of ERK1/2 were increased in Group B and C, and dramatic increased after ITF treatment (in GroupD and E). No significant difference was observed between Group D, E. which was remarkably stronger than Group A, Group B and C.Conclusions: ITF can decrease the productions of PGE2 and TXB2 which reveal the protective effect of ITF on NEC. ITF can increase the Phosphorylation of ERK1/2, active the ERK1/2 pathway, which may be underlying the signal transduction mechanisms of ITF on NEC.