Effects of recombinant human betadefensin3 in neonatal rats with necrotizing enterocolitis

Abstract

Objective To evaluate the beneficial effects of recombinant human betadefensin3 (rhBD3) in neonatal rats with necrotizing enterocolitis (NEC). Methods A total of 68 newborn SpragueDawley rats were randomly divided into 4 groups of control (n=12), control+ rhBD3 (n=12), NEC (n=20) and NEC+ rhBD3 (n=24). The former two groups were maternally fed. Experimental NEC was induced by the exposures to hypertonic feeding, asphyxia and hypothermia. And rhBD3 (100 μg/kg with a daily volume of 0.1 ml) was administered via a gastric tube. Body weight, histological score, survival time, cytokine expression and mucosal integrity were evaluated. Results The group NEC+ hBD3maintained body weight. And rhBD3 dosing decreased the incidence of NEC from 80% in group NEC to 50% in group NEC+ hBD3 (P=0.039), boosted the survival rate from 25% in group NEC to 62.5% in group NEC+ hBD3 (P<0.001) and reduced the severity of NEC (mean NEC scores: 2.50 and 1.67 respectively, P=0.01). Moreover, rhBD3 reduced the expressions of proinflammatory cytokines (TNF-alpha, IL-6) in ileum and sera. And the serum level of diamine oxidase (DAO) and the expression of ZO-1 were also evaluated. Decreased DAO activity was detected in group NEC. And rhBD3 treatment increased the serum concentration of DAO and upregulated the expression of ZO-1. Conclusions rhBD3 protects newborn rats from NEC due to lower levels of inflammatory mediators and preserved mucosal integrity. Key words: Betadefensins; Enterocolitis, necrotizing; Inflammatory mediators