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
NETL
NSTL
万方数据
