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表皮生长因子对宫内生长迟缓兔模型小肠钠/葡萄糖共转运蛋白1表达的影响

Effect of epidermal growth factor on small intestinal sodium/glucose cotransporter-1 expression in a rabbit model of intrauterine growth retardation.

作者信息

Cellini Christina, Xu Jian, Buchmiller-Crair Terry

机构信息

Division of Pediatric Surgery, Children's Hospital of New York Presbyterian, Weill Medical College of Cornell University, New York, NY 10021, USA.

出版信息

J Pediatr Surg. 2005 Dec;40(12):1892-7. doi: 10.1016/j.jpedsurg.2005.08.049.

DOI:10.1016/j.jpedsurg.2005.08.049
PMID:16338313
Abstract

INTRODUCTION

Intrauterine growth-retarded (IUGR) infants have impaired gastrointestinal function with feeding difficulties and predisposition to necrotizing enterocolitis. The rabbit provides a model of IUGR based on uterine position. Sodium/glucose cotransporter-1 (SGLT-1) is a membrane protein responsible for carbohydrate transport across the intestinal brush border membrane. Previous studies demonstrate increases in small intestinal (SI) nutrient uptake in response to amniotic fluid supplementation with epidermal growth factor (EGF). To determine whether SGLT-1 expression plays a role in the intestinal response to EGF supplementation, this IUGR rabbit model was evaluated.

METHODS

Eight pregnant rabbits underwent placement of intraamniotic catheters into 2 normal (Nl) and 2 IUGR fetuses per mother on gestational day 24. Mini-osmotic pumps infused either EGF (300 microg/kg per day) or control solution forming 4 study groups (EGF-Nl vs Cont-Nl; EGF-IUGR vs Cont-IUGR). On gestational day 31, the fetal SI was harvested. Sodium/glucose cotransporter-1/glyceraldehyde-3-phosphate dehydrogenase messenger RNA (mRNA) densitometric band ratios were measured by reverse transcriptase polymerase chain reaction. Immunohistochemistry SGLT-1 staining was performed on middle SI. Statistical analysis was performed using the analysis of variance.

RESULTS

Sodium/glucose cotransporter-1 was expressed in the gastrointestinal tract throughout the last one third of gestation. There were no native differences in SGLT-1 mRNA expression between Nl and IUGR fetuses at term. Epidermal growth factor infusion did not significantly affect SI SGLT-1 mRNA expression in either Nl or IUGR fetuses vs controls (EGF-Nl = 1.94 vs Cont-Nl = 1.94, P = .98; EGF-IUGR = 1.77 vs Cont-IUGR = 1.85, P = .74). Immunohistochemistry revealed increased SGLT-1 SI protein expression in infused IUGR fetuses.

CONCLUSIONS

Increases in previously documented up-regulation in SI nutrient transport after EGF infusion are independent of SGLT-1 mRNA expression. Further studies are warranted investigating SGLT-1 protein expression, localization, and functional kinetics in response to amniotic fluid supplementation with EGF.

摘要

引言

宫内生长受限(IUGR)婴儿存在胃肠功能受损,伴有喂养困难且易患坏死性小肠结肠炎。兔子可提供基于子宫位置的IUGR模型。钠/葡萄糖共转运蛋白-1(SGLT-1)是一种膜蛋白,负责碳水化合物跨小肠刷状缘膜的转运。先前的研究表明,羊水中补充表皮生长因子(EGF)后,小肠(SI)对营养物质的摄取会增加。为了确定SGLT-1表达在小肠对EGF补充的反应中是否起作用,对该IUGR兔子模型进行了评估。

方法

8只怀孕兔子在妊娠第24天接受羊膜腔内导管置入,每只母兔的2个正常(Nl)胎儿和2个IUGR胎儿各置管1根。微型渗透泵输注EGF(300微克/千克/天)或对照溶液,形成4个研究组(EGF-Nl与Cont-Nl;EGF-IUGR与Cont-IUGR)。在妊娠第31天,采集胎儿的SI。通过逆转录聚合酶链反应测量钠/葡萄糖共转运蛋白-1/甘油醛-3-磷酸脱氢酶信使核糖核酸(mRNA)光密度带比。对SI中部进行SGLT-1免疫组织化学染色。采用方差分析进行统计分析。

结果

在妊娠最后三分之一期间,SGLT-1在胃肠道中均有表达。足月时,Nl和IUGR胎儿之间SGLT-1 mRNA表达无天然差异。与对照组相比,输注EGF对Nl或IUGR胎儿的SI SGLT-1 mRNA表达均无显著影响(EGF-Nl = 1.94 vs Cont-Nl = 1.94,P = 0.98;EGF-IUGR = 1.77 vs Cont-IUGR = 1.85,P = 0.74)。免疫组织化学显示,输注EGF的IUGR胎儿SI中SGLT-1蛋白表达增加。

结论

先前记录的EGF输注后SI营养物质转运上调与SGLT-1 mRNA表达无关。有必要进一步研究SGLT-1蛋白表达、定位以及对羊水中补充EGF的功能动力学反应。

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