FETAL ADAPTATION TO CHRONIC UTERINE BLOOD FLOW REDUCTION

胎儿对慢性子宫血流量减少的适应

• 批准号: 2194595
• 负责人: DAVID W BOYLE
• 金额: $ 8.41万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2194595
• 关键词: Fick method; blood flow measurement; embryo /fetus cell /tissue; embryo /fetus hypoxia; gel electrophoresis; insulinlike growth factor; model design /development; pregnancy circulation disorder; prenatal growth disorder; protein biosynthesis; protein metabolism; radiotracer; respiratory gas analyzer; scintillation counter; sheep; stable isotope; statistics /biometry; striated muscles

Intrauterine growth retardation is a significant cause of perinatal morbidity and mortality. Maternal conditions which results in reduced uteroplacental blood flow are consistently associated with fetal growth retardation. The fetal metabolic adaptations which occur under these conditions ensure survival of the fetus at he expense of growth. The purpose of the present investigation is to elucidate the mechanisms responsible for the adaptations which impact on fetal growth. The proposed studies will examine the following hypotheses: 1) fetal hypoxia due to uteroplacental blood flow reduction will decrease tissue insulin like growth factor I (IGF-I) bioactivity which in turn will effect a decrease in protein synthesis and accretion in selected tissues (skeletal muscle), resulting in deceleration in growth rate. 2) the changes in IGF- I bioactivity and protein metabolism can be reserved, at least in part, through maternal (and thereby fetal) oxygen supplementation. 3) infusion of IGF-I into the fetal hindlimb will result in increased protein synthesis in skeletal muscle tissue. These hypotheses will be tested using a model of prolonged uteroplacental blood flow reduction in the sheep developed by the candidate. Daily measurements of linear fetal growth will be made before and during 14 days of uteroplacental blood flow reduction during which time the rates of protein synthesis, breakdown, oxidation and net accretion in the whole fetal body as well as in fetal skeletal muscle will be determined using stable and radioactive tracer methodology. Skeletal muscle metabolism will be examined using an in vivo fetal hindlimb. These studies will provide a broader understanding of the metabolic processes which contribute to the development of fetal growth retardation, thereby possibly stimulating new approaches to the prevention and treatment of this condition in human pregnancies.

胎儿宫内发育迟缓是围产儿死亡的重要原因 发病率和死亡率。 产妇条件，导致减少 子宫胎盘血流量与胎儿生长一致相关 迟钝 在这些条件下发生的胎儿代谢适应 以牺牲生长为代价来保证胎儿的存活。 的 本研究的目的是阐明机制， 负责影响胎儿生长的适应性。 的 拟议的研究将检验以下假设：1）胎儿缺氧 由于子宫胎盘血流减少， 类似生长因子I（IGF-I）的生物活性，这反过来会影响 在选定的组织（骨骼）中减少蛋白质合成和增加 肌肉），导致生长速度减慢。2)IGF的变化- I生物活性和蛋白质代谢可以至少部分地保留， 通过母体（以及胎儿）的氧气补充。3)输注 IGF-I进入胎儿后肢将导致蛋白质增加， 骨骼肌组织中的合成。 这些假设将得到检验 使用子宫胎盘血流减少模型， 候选人开发的羊。 线性胎儿的每日测量 生长将在子宫胎盘血的14天之前和期间进行 在此期间蛋白质合成的速率， 分解、氧化和净增长在整个胎儿的身体以及 如在胎儿骨骼肌中，将使用稳定和 放射性示踪剂法 骨骼肌的新陈代谢将会 使用体内胎儿后肢检查。 这些研究将提供对代谢的更广泛的理解。 有助于胎儿生长发育的过程 阻碍，从而可能刺激新的方法， 预防和治疗人类妊娠中的这种情况。