MAGNETIC RESONANCE SPECTROSCOPY OF THE HUMAN PLACENTA

人胎盘的磁共振波谱检查

基本信息

批准号：
2774239
负责人：
HELEN H. KAY
金额：
$ 10.08万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-07-01 至 1999-03-31
项目状态：
已结题

项目摘要

This application proposes to study human placental metabolism, specifically, energy and carbohydrate metabolism which are fundamental processes necessary to ensure normal fetal well being. Previous reports, as well as our own studies, indicate the placenta favors oxidative phosphorylation under aerobic conditions, but its large glucose consumption and lactate production suggest glycolysis is also an important pathway. However, the amount of lactate and the low total energy produced could not support glycolysis as the major metabolic pathway. The relative importance of each in normal and abnormal placentas is unknown. We would like to test the hypothesis that oxidative phosphorylation and glycolysis are both active metabolic pathways in normal placentas but that diabetic placentas may favor increased glycolysis because of chronic exposure to high levels of glucose and localized hypoxia. Changes in energy metabolism in diabetic placentas may be associated with altered placental functions leading to clinically observed poor fetal outcomes. Placental metabolism studies will be performed using magnetic resonance spectroscopy (MRS) a technique which allows noninvasive, continuous observations of dynamic biochemical processes. Our laboratory has established the use of MRS to study placental villi within a perifusion apparatus. The villi are suspended in medium and viably maintained for several hours by continuous oxygenation, nutrient perifusion, pH and temperature control. Changes in the ATP, inorganic phosphate, and sugar phosphate peaks representing ongoing oxidative phosphorylation and glycolysis have been observed. We have also monitored tissue function by evaluating glucose and oxygen consumption, lactate production. and estradiol, progesterone and chorionic gonadotropin secretion. We will begin by characterizing the roles of oxidative phosphorylation and glycolysis in normal placentas. Metabolic behavior will be monitored under baseline conditions and stressed conditions such as hypoxia, hyper and hypoglycemia, and acidosis. Additional observations will be made of the responses to inhibitors such as cyanide and iodoacetate. We will observe spectroscopic changes in the viable tissue as well as in perchloric acid tissue extracts which yield better resolved spectra at fixed time points. Parallel assessment of placental function will include monitoring chorionic gonadotropin, estradiol and progesterone secretion, glucose and oxygen consumption and lactate production. Once the behavior of normal villi is established under these conditions, diabetic placentas will be studied under the same conditions and comparative analysis will be performed. We hope to acquire a better understanding of normal and diabetic placental energy and carbohydrate metabolism by using the powerful noninvasive method of MRS. Information gained will not only have potential clinical significance but may also represent important complements to future in vivo spectroscopic studies of the placenta.

该申请旨在研究人类胎盘代谢，具体来说，能量和碳水化合物代谢是基础确保胎儿正常健康所必需的过程。以前的报告以及我们自己的研究表明胎盘有利于有氧条件下会发生氧化磷酸化，但其量大葡萄糖消耗和乳酸产生表明糖酵解也的一条重要途径。然而，乳酸含量和总量较低产生的能量不能支持糖酵解作为主要代谢途径。正常和异常情况下各自的相对重要性胎盘未知。我们想检验以下假设：氧化磷酸化和糖酵解都是活跃的代谢正常胎盘中的途径，但糖尿病胎盘可能有利于由于长期接触高水平的糖酵解而增加葡萄糖和局部缺氧。糖尿病患者能量代谢的变化胎盘可能与胎盘功能改变有关临床观察到不良胎儿结局。将使用磁共振进行胎盘代谢研究光谱学 (MRS) 是一种允许非侵入性、连续的技术动态生化过程的观察。我们实验室有建立了使用 MRS 研究灌注内胎盘绒毛的方法设备。绒毛悬浮在培养基中并可有效维持通过连续氧合、营养物灌注、pH 和温度控制。 ATP、无机磷酸盐和糖的变化磷酸盐峰代表正在进行的氧化磷酸化和已观察到糖酵解。我们还监测了组织功能通过评估葡萄糖和氧的消耗、乳酸的产生。和雌二醇、黄体酮和绒毛膜促性腺激素的分泌。我们将首先描述氧化磷酸化的作用和正常胎盘中的糖酵解。代谢行为将是在基线条件和压力条件下进行监测，例如缺氧、高血糖、低血糖以及酸中毒。额外的观察结果将由对氰化物等抑制剂的反应组成碘乙酸盐。我们将观察活组织的光谱变化以及高氯酸组织提取物，其产量更好在固定时间点解析光谱。胎盘的平行评估功能包括监测绒毛膜促性腺激素、雌二醇和黄体酮分泌、葡萄糖和耗氧量以及乳酸生产。一旦正常绒毛的行为在以下条件下建立在这些条件下，糖尿病胎盘将在相同的条件下进行研究并进行条件比较分析。我们希望更好地了解正常和糖尿病胎盘能量使用强大的非侵入性方法进行碳水化合物代谢夫人的。获得的信息不仅具有潜在的临床意义意义重大，但也可能代表对未来的重要补充胎盘的体内光谱研究。