Protective effect of deferoxamine on necrotizing colitis in neonatal rats
Objective To explore the protective effect and molecular mechanism of deferoxamine on necrotizing colitis in neonatal rats.Methods A total of 30 SD neonatal rats were randomly divided into a control group,a model group,and a deferoxamine group using a random number table method,with 10 rats in each group.The rats in the model group and deferoxamine group were given conventional formula milk by gavage to establish a necrotizing colitis model,while neonatal rats in the control group were given rat milk.The neonatal rats in the deferoxamine group were given 30 mg/(kg·d)deferoxamine by gavage,while the control group and model group were given equal volume of physiological saline.After 4 days of treatment,the general conditions of rats in the three groups were observed.The intestinal pathological changes of rats in the three groups were analyzed using hematoxylin eosin(HE)staining.The expression levels of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin(IL)-12 and IL-18]in intesti-nal tissue of three groups were tested using enzyme-linked immunosorbent assay.The levels of oxidative stress indicators in the intestinal tissues of three groups were analyzed using immunoassay.The expression levels of glutathione peroxidase 4(GPX4)and cysteine/glutamate reverse transporter(SLC7A11)in intes-tinal tissue were analyzed by Western blotting.The CXC tchemokine ligand 1(CXCL1)and CXC chemo-kine receptor 2(CXCR2)mRNA expression levels in intestinal tissue were analyzed by fluorescence quanti-tative polymerase chain reaction(PCR).The comparison of inter group econometric data was conducted u-sing one-way analysis of variance.Results The weight change of the rats in the deferoxamine group[(1.11±0.11)g]was significantly greater than that of the newborn rats in the model group[(0.55± 0.11)g,t=11.220,P＜0.05].The disease activity index score of neonatal rats in the deferoxamine group(1.80±0.79)was significantly lower than that in the model group(3.70±1.06,t=4.549,P＜0.05).The levels of inflammatory factors(TNF-α,IL-12 and IL-18)in the intestinal tissue of neonatal rats treated with deferoxamine[(45.63±11.32),(40.03±5.97),(67.62±7.27)pg/ml]were significantly lower than those in the model group[(84.60±12.20),(73.89±13.48),(107.59±12.22)pg/ml,t=7.025,6.890,8.437,P＜0.05].The mRNA expression levels of CXCL1 and CXCR2 in the intestinal tissue of neonatal rats in the deferoxamine group(1.36±0.12,1.35±0.09)were significantly lower than those in the model group(1.80±0.14,1.85±0.08,t=6.968,11.970,P＜0.05).The levels of SOD and GSH-PX activity in the intestinal tissue of neonatal rats in the deferoxamine group[(45.65±9.27),(47.53±6.78)U/mg]were significantly higher than those in the model group[(26.86±4.51),(22.74±3.79)U/mg,t=5.468,9.571,P＜0.05].The expression levels of GPX4 and SLC7A11 pro-teins in the intestinal tissue of neonatal rats in the deferoxamine group(0.89±0.04,0.64±0.06)were significantly higher than those in the model group(0.51±0.19,0.38±0.11)(t=5.571,6.174,P＜0.05).Conclusion Deferoxamine can significantly inhibit ferroptosis,reduce intestinal inflammation,and thus protect colon tissue.
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