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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。胎儿宫内发育受限是导致围产儿发病率和死亡率的重要原因之一。近年来，人们越来越关注IUGR妊娠时通过胎盘的氨基酸转运减少这一具体缺陷。在发育迟缓的人类妊娠中，无论是在宫内采集胎儿血液时还是在剖腹产时，都显示出胎盘氨基酸转运的减少。这些发现得到了对妊娠合并IUGR胎盘的体外研究的支持。A系统(1)运输的氨基酸在这些妊娠中显示出特定的减少。虽然已经有许多关于氨基酸在灌流的人胎盘(2-4)和我们的胎盘微囊制剂(5，6)中转运的研究，但还没有描述体内的转运特性。我们实验室最近在怀孕绵羊身上进行的体内研究表明，九种必需氨基酸在体内的转运速度有显著差异(15)。本研究的目的是分析所有必需氨基酸在体内的转运。我们认为，这些研究应该确定一种必需的氨基酸，它将是胎盘衰竭的敏感指标，从长远来看，可能会为IUGR妊娠的治疗提供额外的非常有用的指导。人类妊娠合并IUGR的胎盘血管结构异常[17-23]，包括异常的分支模式。用扫描电子显微镜(SEM)对正常和病理胎盘的胎盘血管铸型进行了成像。已经观察到了特征性的血管改变，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令人困惑。胎盘是一个异质器官，血管铸型的扫描电子显微镜可能只代表局灶性变化。作为这项研究的第二个目标，我们希望评估两种技术的使用，即使用三维成像软件重建的钡-明胶动脉造影术(24)和连续组织切片(25)，以了解这些技术是否可以作为评估妊娠合并IUGR的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.