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.

该应用建议研究人胎盘代谢，具体而言，能量和碳水化合物代谢是基本的确保正常胎儿健康所需的过程。以前的报告以及我们自己的研究表明了胎盘偏爱有氧条件下的氧化磷酸化，但其大葡萄糖消耗和乳酸的产生表明糖酵解也是一个重要的途径。但是，乳酸的量和总数低产生的能量不能支持糖酵解作为主要代谢路径。每个人在正常和异常中的相对重要性胎盘是未知的。我们想检验以下假设氧化磷酸化和糖酵解都是活性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暴露于高水平的糖酵解增加葡萄糖和局部缺氧。糖尿病中能量代谢的变化胎盘可能与胎盘功能变化有关临床观察到的胎儿结局不佳。胎盘代谢研究将使用磁共振进行光谱法（MRS）一种允许无创，连续的技术动态生化过程的观察。我们的实验室有建立了MRS在促进中研究胎盘绒毛的使用设备。绒毛被悬挂在中等中连续氧合，营养促进，pH和pH和温度控制。 ATP，无机磷酸盐和糖的变化代表持续氧化磷酸化的磷酸盐峰和已经观察到糖酵解。我们还监视了组织功能通过评估葡萄糖和氧气消耗，乳酸产生。和雌二醇，孕酮和绒毛膜促性腺激素分泌。我们将首先表征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监测缺氧，高血糖症和酸中毒。其他观察结果将由对氰化物等抑制剂的反应制成碘乙酸。我们将观察到可行组织的光谱变化以及在氯酸组织提取物中产生更好的在固定时间点解析了光谱。胎盘的平行评估功能将包括监测绒毛膜促性腺激素，雌二醇和孕酮分泌，葡萄糖和氧气消耗和乳酸生产。一旦建立了正常绒毛的行为这些条件，将在同一情况下研究糖尿病胎盘将进行条件和比较分析。我们希望更好地了解正常和糖尿病胎盘能量和使用强大的无创方法和碳水化合物代谢太太。获得的信息不仅将具有潜在的临床意义，但也可能代表着对未来的重要补充胎盘的体内光谱研究。