DETERMINATION OF RATES OF IN-VIVO PLACENTAL TRANSPORT OF 9 ESSENTIAL AMINO ACIDS

9 种必需氨基酸体内胎盘转运速率的测定

• 批准号: 7374335
• 负责人: FREDERICK C BATTAGLIA
• 金额: $ 3.99万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-24 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374335
• 关键词: human; placenta; pregnancy; reduction

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Intrauterine growth restriction represents one of the most important causes of perinatal morbidity and mortality. In recent years, there has been an increased focus on the specific defect of a reduction in amino acid transport across the placenta in IUGR pregnancies. A reduction in placental transport of amino acids has been shown in growth retarded human pregnancies, both at the time of in utero fetal blood sampling and at Cesarean section. These findings are supported by in vitro studies of placentas from pregnancies complicated by IUGR. A specific reduction in these pregnancies has been shown for amino acids transported by System A (1). While there have been numerous studies of amino acid transport in perfused human placentas (2-4) and in our microvesicle preparations of the placenta (5,6), in vivo transport characteristics have not been described. In vivo studies carried out in pregnant sheep recently in our laboratory have shown striking differences in the rates of in vivo transport among the nine essential amino acids (15). The goal of the present study is to analyze the in vivo transport for all essential amino acids. It is our belief that these studies should identify an essential amino acid that would be a sensitive index of placental failure and in the long term may provide an additional very useful guide in the management of IUGR pregnancies. Human pregnancies complicated by IUGR have been shown to have abnormal placental vasculature [17-23] including abnormal branching patterns. Human placental vascular casts have been imaged using scanning electron microscopy (SEM) in both normal and pathologic placentas. Characteristic vascular changes have been observed, but there is little clinical correlation with doppler studies and clinical terms are often inconsistent or confusing. The placenta is a heterogeneous organ and SEM of vascular casts may be representative of focal changes only. As a second goal of this study we wish to evaluate the use of two techniques, barium-gelatin arteriograms (24) and serial tissue sections that have been reconstructed using 3-dimesional imaging software (25), to see if these could be useful tools in the evaluation of the placental vasculature in human pregnancies complicated by IUGR.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。宫内生长受限是围产期发病和死亡的最重要原因之一。近年来，人们越来越关注IUGR妊娠中氨基酸转运减少的特定缺陷。在发育迟缓的人类妊娠中，无论是在子宫内取样胎儿血液时还是在剖宫产时，都显示出胎盘氨基酸运输的减少。这些发现得到了IUGR合并妊娠胎盘的体外研究的支持。由A系统运输的氨基酸在这些妊娠中有特定的减少(1)。虽然已经有很多关于氨基酸在灌注的人胎盘中的转运的研究（2-4）和我们的胎盘微泡制剂（5,6），但体内转运特性尚未被描述。最近在我们实验室对怀孕绵羊进行的体内研究表明，九种必需氨基酸的体内转运速率存在显著差异（15）。本研究的目的是分析所有必需氨基酸的体内转运。我们相信，这些研究应该确定一种必需氨基酸，它将是胎盘衰竭的敏感指标，从长远来看，可能为IUGR妊娠的管理提供额外的非常有用的指导。人类妊娠合并IUGR已被证明有异常的胎盘血管[17-23]，包括异常的分支模式。用扫描电镜对正常和病理胎盘的人胎盘血管模型进行了成像。特征性血管改变已被观察到，但与多普勒研究的临床相关性很小，临床术语常常不一致或混淆。胎盘是一个异质器官，血管铸型的扫描电镜可能仅代表局灶性变化。作为本研究的第二个目标，我们希望评估两种技术的使用，钡明胶动脉造影（24）和使用三维成像软件重建的连续组织切片（25），看看它们是否可以作为评估人类妊娠合并IUGR胎盘血管系统的有用工具。