β-胡萝卜素对坏死性小肠结肠炎新生小鼠肠道氧化应激的保护作用

Protective effect ofβ-caroteneupon intestinal oxidative stress in newborn mice with necrotizing enterocolitis

目的运用坏死性小肠结肠炎(necrotizing enterocolitis,NEC)新生小鼠模型,探讨β-胡萝卜素对NEC新生小鼠肠道损伤的作用。方法选用5日龄C57BL/6新生小鼠15只,按随机数字法分为三组,每组5只。对照组:母鼠哺乳喂养,无其他任何干预;NEC组:通过对新生小鼠缺氧刺激,人工喂养及脂多糖干预诱导产生NEC;β-胡萝卜素干预组:在诱导产生NEC的同时,给予新生小鼠胃管灌注β-胡萝卜素(1 mg/kg)。于生后第9日收集各组新生小鼠末端回肠组织,分析比较NEC病理评分,肠道炎症反应,肠上皮细胞增殖、凋亡及氧化应激水平。结果与对照组相比,NEC组肠道出现明显损伤(0/5比5/5,P<0.05),炎症反应(1.0122±0.03比9.5367±3.025,P<0.01)及氧化应激水平(TBARS 6.9292±0.129比11.4420±0.074,P<0.01;GPx 25.21±7.113比17.5674±5.769,P<0.01)明显升高,肠上皮细胞增殖能力下降(5.36±0.308比1.48±0.212,P<0.01),且凋亡增多(2.5683±0.39比5.4974±0.967,P<0.01);与NEC组相比,β-胡萝卜素干预组的肠道组织损伤程度明显降低(5/5比1/5,P<0.05),肠道组织炎症减轻(9.5367±3.025比5.7871±1.489,P<0.01),氧化应激水平明显下降(TBARS 11.4420±0.074比8.1148±0.013,P<0.01;GPx 17.5674±5.769比35.1576±11.077,P<0.01),肠道上皮细胞增殖能力增强(1.48±0.212比3.8±0.1,P<0.01),凋亡减少(5.4974±0.967比3.7773±0.772,P<0.05);干预组肠道组织损伤程度及凋亡水平较NEC组有所改善的同时,与对照组比较差异无统计学意义(P>0.05)。结论β-胡萝卜素可通过降低肠道氧化应激水平来减轻NEC新生小鼠肠道损伤程度,缓解肠道炎症反应,促进肠上皮细胞增殖并抑制细胞凋亡。提示β-胡萝卜素对NEC新生小鼠肠道损伤具有保护作用。

Objective To explore the function ofβ-carotene in a newborn murine model of necrotizing enterocolitis(NEC).Methods A total of 15 five-day-old C57BL/6 mice were divided randomly into 3 groups(n=5 each).Control group:neonatal mice were raised by adult mice;NEC group:mice were stimulated for NEC modeling by oxygen deficit,artificial feeding and lipopolysaccharide(LPS)intervention;β-carotene intervention group:apart from stimuli of NEC modeling,1 mg/kg body weightβ-carotene was given daily to neonatal mice.At Day 9 after birth,terminal ileum tissues of neonatal mice were harvested and pathological scores,inflammation level,enterocyte proliferation,apoptosis and oxidative stress level were estimated.Results As compared to control group,apparent injury(0/5 vs.5/5,P<0.05),high level of inflammation(1.0122±0.03 vs.9.5367±3.025,P<0.01)and oxidative stress(TBARS 6.9292±0.129 vs.11.4420±0.074,P<0.01;GPx 25.21±7.113 vs.17.5674±5.769,P<0.01),lower proliferation(P<0.01)and more apoptotic cells were found in NEC group(P<0.01);while inβ-carotene intervention group,relative to NEC group,injury grade(5/5 vs.1/5,P<0.05),inflammation(9.5367±3.025 vs.5.7871±1.489,P<0.01)and oxidative stress level(TBARS 11.4420±0.074 vs.8.1148±0.013,P<0.01;GPx 17.5674±5.769 vs.35.1576±11.077,P<0.01)and apoptotic cells declined(5.4974±0.967 vs.3.7773±0.772,P<0.05),but on the contrary,proliferative capability of intestine improved apparently(1.48±0.212 vs.3.8±0.1,P<0.01).In addition,compared with control group,no significant difference existed in the level of intestinal tissue injury or apoptosis inβ-carotene intervention group(P>0.05).Conclusionsβ-carotene can alleviate the intestinal damage of NEC newborn mice by reducing the level of intestinal oxidative stress and inflammation,promoting intestinal epithelial cell proliferation and inhibiting apoptosis.It hints thatβ-carotene has a protective effect upon intestinal injury of NEC newborn mice.