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.

该项目建议研究人类胎盘代谢， 基本的能量和碳水化的代谢是基本的 确保正常胎儿健康所需的过程。 胎盘 有氧条件下有利于氧化磷酸化，但 大量的葡萄糖消耗和乳酸的产生表明糖酵解是 也是一个重要的途径。 每条途径的相对重要性 正常和异常胎盘尚不清楚。 我们想测试 假设氧化磷酸化和糖酵解都是 正常胎盘中的主动代谢途径，但异常 胎盘，即糖尿病胎盘，可能有利于增加糖酵解 由于长期暴露于高水平的葡萄糖和局部 缺氧。 糖尿病胎盘中能量代谢的变化可能是 与改变胎盘功能的改变有关 观察到的胎儿结局不佳。 胎盘代谢研究将是 使用磁共振光谱（MRS）进行的观察 动态生化过程无创，连续。 太太 将用于研究促进设备中的胎盘绒毛。 绒毛被悬挂在中等中，并通过几个 通过连续氧合，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 将观察到糖酵解。 组织功能将通过 监测葡萄糖和氧气消耗，乳酸，乳酸 脱氢酶，雌二醇，孕酮和绒毛膜促性腺激素 发布。 我们将表征氧化磷酸化的作用 在基线条件下的正常胎盘中的糖酵解，例如 缺氧，高血糖症和酸中毒。 对 将观察到氰化物和碘乙酸等抑制剂。 我们将 进行可行组织以及高氯酸的光谱法 在固定时间产生更好分辨光谱的组织提取物 点。 在正常建立绒毛行为之后 实验条件，将研究糖尿病胎盘 进行了类似的条件和比较分析。 我们希望 更好地了解正常和糖尿病胎盘能量 和使用强大的非侵入性方法 太太。 获得的信息不仅将具有潜在的临床 意义，但也可能代表对未来的重要补充 胎盘的体内光谱研究。