Abstract：OBJECTIVE: Necrotizing enterocolitis (NEC) is a common severe gastrointestinal disorder in premature infants. Reactive oxygen species (ROS) has been proved to have a close relationship with the pathogenesis of NEC. This study aimed to explore the relationship between xanthine oxidase (XO), one of the major sources of ROS, and intestinal injury using a neonatal rat model of NEC. METHODS: Forty-eight newborn rats were assigned randomly into two groups: NEC group (n=40, 8 each time point) and Control group (n=8). The rats of the NEC group were given gastric lavage with 5 mg/kg E coli O_ 55∶B_5 endotoxin (LPS) dissolved in 0.2 mL normal saline. The rats of the Control group received gastric lavage treatment with 0.2 mL normal saline alone, and were sacrificed 3 hrs later. The NEC rats were sacrificed 3, 6, 12, 24, and 72 hrs after treatment respectively. A part of lower ileum was removed, fixed, embedded in paraffin.and stained with hematoxylin and eosin for histological evaluation. The rest of the ileum was frozen in liquid nitrogen for XO activity measurements. The correlation between the histological changes and XO activity was studied. RESULTS: The intestinal injury scores were significantly higher in the NEC group 3, 6, 12 and 24 hrs after treatment (1.54±0.87, 1.79±0.75, 1.92±0.43 and 2.29±0.60) than that of the Control group (0.08±0.15) (P<0.05). Increased XO levels were observed in the NEC group at each time point (1.15±0.09, 1.24±0.15, 1.30±0.18 and 1.42±0.21 U/mgprot) when compared with that of the Control group (0.95±0.13 U/mgprot) (P<0.05). Spearman correlation analysis showed a significantly positive correlation between XO levels and intestinal injury scores within 24 hrs of LPS treatment . CONCLUSIONS: XO may play an important role in the development of necrotizing enterocolitis.
