Protective effect of butyrate on neonatal necrotizing enterocolitis and its molecular mechanism
Objective To investigate the protective effect of butyric acid on neonatal necrotizing enterocolitis and its molecular mechanism.Methods 45 BALB/c newborn mice were divided into control group,model group and butyric acid group according to random number table method,15 mice/per group.The model group and butyric acid group were fed with formula milk to establish necrotic enterocolitis mod-el,while the control group was fed normally.The mice in the butyric acid group were given 0.05 ml/g bu-tyrate solution 3 days after birth and were treated continuously for 7 days.The mice in the control group and the model group were given equal volume normal saline.The mice were killed 3 days after modeling,and the colonic histopathological changes were analyzed by hematoxylin-eosin staining.The levels of inflamma-tory factors in the three groups were analyzed by enzyme-linked immunosorbent assay.The apoptosis level of colon tissue cells was used to analyze by terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL)staining.The phosphorylation levels of p38 protein kinase(p38 MAPK)and nuclear transcrip-tion factor(NF-κB)subunits p65 and p50 in colon tissues were analyzed by Western blotting.One-way a-nalysis of variance was used to compare the measurement data between groups.Results The body weight of mice in the model group[(4.87±0.74)g]was lower than that of the control group[(7.27±0.70)g,t=9.081,P＜0.05].The body weight in Butyric acid group[(6.07±0.80)g]significantly lower than the model group mice[(4.87±0.74)g,t=4.260,P＜0.05].The colonic tissue injury score of model group[(3.07±0.96)points]was higher than that of control group[(0.67±0.62)points,t=8.138,P＜0.05].The colonic tissue damage score of mice in butyric acid group[(1.47±0.51)points]was sig-nificantly lower than that in model group[(3.07±0.96)points,t=5.679,P＜0.05].Interleukin1β,tumor necrosis factor a,interleukin6 and interleukin18 in colon tissue of mice in butyric acid group[(64.07±11.44),(54.80±9.37),(49.20±5.72),(36.60+5.17)pg/g]significantly lower than the model group mice[(138.80±17.72),(96.47±8.25),(93.20±12.85),(82.07±9.50)pg/g,t=13.720,12.930,12.110,16.290,P＜0.05].The apoptosis level of colon tissue in butyric acid group[(7.08±0.60)％]was significantly lower than that in model group[(14.51±1.76)％,t=15.510,P＜0.05].The levels of phosphorylated p38 MAPK,phosphorylated NF-κB p65 and phosphoryl-ated NF-κB p50 in colon tissue of butyric acid group(0.68±0.13,0.80±0.09,0.83±0.09)were sig-nificantly lower than those of model group(0.93±0.11,1.22±0.21,1.15±0.15,t=5.994,7.067,13.970,P＜0.05).Conclusion Butyric acid can significantly inhibit p38 MAPK and NF-κB pathways,inhibit the release of inflammatory factors,reduce the death of colonic tissue cells,and play a protective role in neonatal necrotizing enterocolitis.
Butyric acidNeonatal necrotizing enterocolitisp38 protein kinaseNuclear transcription factorInflammation
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