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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 宫内生长受限是围产期发病率和死亡率的最重要原因之一。 近年来，人们越来越关注IUGR妊娠中胎盘氨基酸转运减少的特异性缺陷。 在生长迟缓的人类妊娠中，无论是在子宫内胎儿血液取样时还是在剖腹产时，都显示出氨基酸的胎盘转运减少。 这些发现得到了胎儿宫内发育迟缓胎盘体外研究的支持。 通过系统A转运的氨基酸在这些妊娠中显示出特异性减少（1）。 虽然在灌注的人胎盘（2-4）和我们的胎盘微泡制剂（5，6）中已经有许多关于氨基酸转运的研究，但尚未描述体内转运特征。 最近在我们实验室对怀孕绵羊进行的体内研究表明，9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，这将是一个敏感的指标胎盘衰竭，并在长期内可能提供一个额外的非常有用的指导管理IUGR妊娠。 已显示伴有IUGR的人类妊娠具有异常胎盘血管系统[17-23]，包括异常分支模式。 人胎盘血管铸型已成像扫描电子显微镜（SEM）在正常和病理胎盘。 已经观察到特征性的血管改变，但与多普勒研究的临床相关性很小，临床术语经常不一致或混淆。 胎盘是一个异质性器官，血管铸型的扫描电镜可能仅代表局灶性改变。 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），以了解这些是否可以成为评估合并IUGR的人类妊娠胎盘血管系统的有用工具。

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.