表皮生长因子及其受体在新生鼠肠损伤中的动态变化

目的 检测新生鼠肠损伤时回肠组织表皮生长因子(epidermal growth factor,EGF)、转化生长因子α(transforming growth factor-α,TGF-α)及表皮生长因子受体(epithelial growth factor receptor,EGFR)的动态变化,探讨其在新生儿坏死性小肠结肠炎中的作用. 方法 1日龄新生Wistar大鼠随机分为实验组40只和对照组8只.实验组腹腔注射5 mg/kg内毒素(lipopolysaccharide,LPS),对照组注射同等剂量无菌生理盐水.实验组大鼠于注射LPS后1、3、6、12和24 h处死后分离胃肠道,观察回肠组织形态学改变,测定肠组织EGF、EGFR蛋白表达及EGFR mRNA和TGF-αmRNA的动态变化,并与对照组进行比较. 结果 实验组于注射LPS后1、3、6、12和24 h回肠组织损伤评分分别为(1.28±0.62)分,(1.75±0.74)分,(1.98±0.75)分,(2.85±0.41)分和(2.35±0.63)分,均明显高于对照组(0.12±0.17)分(P<0.01);EGF蛋白水平分别为(235.9±44.3)pg/mgprot,(231.8±30.0)pg/mg prot,(223.3±48.1)pg/mg prot,(211.7±47.0)pg/mg prot和(221.4±39.0)pg/mg prot,显著低于对照组(287.7±42.6)pg/mg prot](P<0.05),EGF浓度与肠损伤程度呈负相关(r=-1.000,P<0.01);注射LPS后EGFR蛋白和mRNA表达增加,但与肠损伤程度无相关性(r=0.800,P>0.05);TGF-α mRNA在注射LPS后1 h和3 h明显上调. 结论 EGF水平降低可能在新生儿坏死性小肠结肠炎发生发展中起关键作用.

Dynamic changes of epidermal growth factor and its receptor in neonatal rats with intestine injury

Objective To determine the dynamic changes of ileum epidermal growth factor(EGF),transforming growth factor-α(TGF-α)and epithelial growth factor receptor(EGFR)in neonatal rats with intestinal injury and to investigate their role in the neonatal necrotizing enterocolitis(NEC). Methods One-day-old Wistar rat pups were divided into two groups.The rats in the lipopolysaccharide(LPS)-injected group(n=40)received an intraperitoneal injection with 5 mg/kg LPS and those in the control group(n=8)did not.Control group and LPS-injected group at 1,3,6,12 and 24 h following LPS challenge were sacrificed for histological evaluation of NEC and for measurernents of EGF,EGFR,EGFR mRNA and TGF-α mRNA. Results Compared with the control group(0.12 0.17).the LPS-iniected pups showed a significant increase in injury scores at 1,3,6,12 and 24 h(1.28±0.62,1.75±0.74,1.98±0.75,2.85±0.41 and 2.35士0.63,respectively)(P<0.01).EGF protein levels at 1,3,6,12,24 h(235.9±44.3)pg/mg prot,(231.8±30.0)pg/mg prot,(223.3±48.1)pg/mg prot,(211.7±47.0)pg/mg prot and(221.4±39.0)pg/mgprot,respectively]were significantly lower than that of the control group(287.7±42.6)pg/mg prot](P<0.05).There was a negative correlation between the EGF levels and the grade of intestinal injury within 24 h(r=1.000,P<0.01).The expression of EGFR protein and mRNA was increased after LPS administration.There was no correlation between the EGFR protein and the grade of intestinal injury(r=0.800,P>0.05).The expression of TGF-α mRNA was significantly up-regulated at 1 and 3 h following LPS injection. Conclusions Reduced levels of EGF may play a pivotal role in the pathogenesis of NEC.