Protective efficiency and mechanism of glutamine on intestinal tissue of neonatal rats with necrotizing enterocolitis

Objective To investigate the protective efficiency and mechanism of glutamine (Gln) in neonatal rats with necrotizing enterocolitis (NEC). Methods Forty-eight neonatal Sprague-Dawley rats were randomly divided into four groups with 12 in each group, including the blank-control group, Gln-control group, NEC group and NEC+Gln group. Blank-control rats were given artificial feeding for three days without any interventions. Gln-control rats were given artificial feeding with 0.3 g/(kg·d) Gln once a day for three days. NEC rats were subject to artificial feeding and cold exposure after hypoxic-reoxygenation twice a day for three days to establish NEC models. NEC+Gln rats were given 0.3 g/(kg·d) Gln once a day for three days while the NEC models were established. The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) protein was detected by immunohistochemistry and the expression of vascular endothelial growth factor receptor-2 (VEGFR-2) mRNA was determined by reverse transcription-polymerase chain reaction. Kruskal-Wallis and Wilcoxon tests were used for statistical analysis. Results Intestinal tissue and weight gain in rats in the blank-control group and Gln-control group were normal. Severe pathological injuries in the intestinal tissue and obvious weight loss were seen in the NEC group, which were alleviated in the NEC+Gln group. The expression index of VEGF in the NEC group was 77.35% (68.70%-86.00%), and was higher than that in the blank-control group [18.92% (15.55%-22.29%), Z=-4.287], Gln-control group [16.92% (13.77%-20.07%), Z=-4.069] and NEC+Gln group [23.83% (19.49%-28.17%), Z=-3.895]. The expression index of VEGF in the NEC+Gln group was higher than that in the Gln-control group (Z=-3.026), all differences were statistically significant (all P<0.008 3). A higher expression index of PCNA was seen in the blank-control group [34.17% (28.39%-39.95%), Z=-3.787], Gln-control group [34.42% (29.04%-39.80%), Z=-3.562] and NEC+Gln group [30.67% (27.53%-33.81%), Z=-3.435] compared with the NEC group [15.00% (13.06%-16.94%)]. The expression index of PCNA in the NEC+Gln group was lower than that in the Gln-control group (Z=-2.827), and was statistically significantly different (all P<0.008 3). VEGFR-2 mRNA levels in the NEC group were 0.1545 (0.1268-0.1822), higher than those in the blank-control group [0.0224 (0.0149-0.0299), Z=-5.028], Gln-control group [0.0189 (0.0148-0.0230), Z=-5.436] and NEC+Gln group [0.0285 (0.0167-0.0402), Z=-4.875]. VEGFR-2 mRNA levels in the NEC+Gln group were higher than that in the Gln-control group (Z=-3.239), and were statistically significantly different (all P<0.008 3). Conclusions Gln protects the intestinal mucosa from injury in NEC rats resulting from down-regulation of the expression of VEGF and up-regulation of PCNA. Key words: Enterocolitis, necrotizing; Glutamine; Animals, newborn; Rats; Disease models, animal