Insulin-like growth factor I reduces the occurrence of necrotizing enterocolitis by reducing inflammatory response and protecting intestinal mucosal barrier in neonatal rats model

OBJECTIVE: To observe the effect of enteral supplement of insulin-like growth factor I (IGF-1) on dynamic changes of TLR4, NF-κB, IL-6, SIgA and MUC2 in intestinal tissues of neonatal rats, and to investigate the protective effects and possible mechanisms of IGF-1 on necrotizing enterocolitis (NEC).

MATERIALS AND METHODS: Specific pathogen free (SPF) neonatal Sprague Dawley (SD) rats aged 3 days old were randomly divided into 3 groups, namely, normal control group, NEC model group and IGF-1 intervention group. In NEC group, the neonatal NEC rat models were established using artificial feeding, hypoxia and cold stimulation. In IGF-1 intervention group, the models were established by means of artificial feeding plus hypoxia and cold stimulation, and IGF-1 (22 ug/L) at a physiological concentration similar to the breast milk was added to milk replacer for intervention. The rats in the three groups were killed after the blood was collected from the heart at 24, 48 and 72 h, respectively, following the establishment of models; then, 3 cm of the terminal ilea were dissected and used for histopathological examination, RT-PCR and ELISA studies after hematoxylin and eosin (HE) staining.

RESULTS: Symptoms in IGF-1 intervention group were significantly relieved, and the incidence rate of NEC was lowered remarkably. In NEC model group, the peak expression of TLR4 mRNA occurred later than that of NF-κB mRNA and IL-6, and the expressions of TLR4 mRNA, NF-κB mRNA and IL-6 were decreased at 72 h after IGF-1 intervention. In NEC model group, the expression of MUC2 showed a transient decrease, the expression of SIgA was on the decline, but the expressions of MUC2 and SIgA were increased after IGF-1 intervention.

CONCLUSIONS: The enteral administration of IGF-1 at a physiological concentration can ameliorate the clinical symptoms in neonatal NEC rat models and decrease the occurrence rate. The possible mechanism is that IGF-1 down-regulates the TLR4 mRNA expression to inhibit the production of inflammatory mediators, and it up-regulates the expressions of MUC2 and SIgA to protect the mechanical and immuno-barrier functions of the intestinal mucous.

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