STUDY OF ENERGY & CARBOHYDRATE METABOLISM IN HUMAN PLACENTAL TISSUE

能源研究

• 批准号: 6298113
• 负责人: HELEN H. KAY
• 金额: $ 0.75万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6298113
• 关键词: biomedical resource; carbohydrates; enzymes; human tissue; mother /infant health care; nuclear magnetic resonance spectroscopy; reproductive system

This project proposes to study human placental metabolism, specifically energy and carbohydrate metabolism which are fundamental processes necessary to ensure normal fetal well being. The placenta favors oxidative phosphorylation under aerobic conditions, but its large glucose consumption and lactate production suggest glycolysis is also an important pathway. The relative importance of each pathway in normal and abnomal 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 abnormal placentas, i.e., 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) which observes dynamic biochemical processes noninvasively and continuously. MRS will be used 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 ATP, inorganic phosphate, and sugar phosphate peaks representing ongoing oxidative phosphorylation and glycolysis will be observed. Tissue function will be evaluated by monitoring glucose and oxygen consumption, and lactate, lactate dehydrogenase, estradiol, progesterone and chorionic gonadotropin release. We will characterize the roles of oxidative phosphorylation and glycolysis in normal placentas under baseline conditions such as hypoxia, hyper and hypoglycemia, and acidosis. Responses to inhibitors such as cyanide and iodoacetate will be observed. We will perform spectroscopy of viable tissue as well as perchloric acid tissue extracts which yield better resolved spectra at fixed time points. After establishing villous behavior under normal and experimental conditions, diabetic placentas will be studied under similar conditions and comparative analysis performed. We hope to acquire a better understanding of normal and diabetic placental energy and carbyhydrate 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.

该项目旨在研究人类胎盘代谢， 特别是能量和碳水化合物代谢，这是基础 确保胎儿正常健康所必需的过程。 胎盘 有氧条件下有利于氧化磷酸化，但其 大量的葡萄糖消耗和乳酸产生表明糖酵解是 也是一条重要途径。 每个途径的相对重要性 正常和异常胎盘尚不清楚。 我们想测试一下 假设氧化磷酸化和糖酵解都是 正常胎盘中活跃的代谢途径，但异常胎盘 胎盘，即糖尿病胎盘，可能有利于糖酵解增加 由于长期暴露于高水平的葡萄糖和局部 缺氧。 糖尿病胎盘能量代谢的变化可能是 与胎盘功能改变有关，导致临床上 观察到胎儿结局不佳。 胎盘代谢研究将 使用磁共振波谱 (MRS) 进行观察 无创且连续的动态生化过程。 太太 将用于研究灌注装置内的胎盘绒毛。 绒毛悬浮在培养基中并可存活数年 小时通过连续氧合、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 将观察到糖酵解。 组织功能将通过以下方式评估 监测葡萄糖和耗氧量以及乳酸、乳酸 脱氢酶、雌二醇、黄体酮和绒毛膜促性腺激素 发布。 我们将描述氧化磷酸化的作用 和正常胎盘在基线条件下的糖酵解，例如 缺氧、高血糖、低血糖以及酸中毒。 回应 将观察到氰化物和碘乙酸盐等抑制剂。 我们将 对活组织以及高氯酸进行光谱分析 组织提取物在固定时间产生更好的分辨率光谱 点。 在正常和正常情况下建立绒毛行为后 实验条件，糖尿病胎盘将在以下条件下进行研究 相似条件下进行比较分析。 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，但也可能是对未来的重要补充 胎盘的体内光谱研究。