MATERNAL DIET AND PROGENY RENAL INJURY

母亲饮食与后代肾损伤

• 批准号: 3327829
• 负责人: Silvia H Azar
• 金额: $ 13.51万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3327829
• 关键词: blood pressure; developmental nutrition; dietary proteins; growth /development; infant animal; kidney circulation; kidney function; laboratory rat; lactation; micropuncture; mother /embryo /fetus nutrition; nephrectomy; nutrition related tag; perinatal; pregnancy; proteinuria; salt intake

DESCRIPTION (Principal Investigator's Abstract): Some populations ingesting low protein-high salt diets show a high incidence of end stage renal failure due to glomerulonephritis, diabetes, and hypertension. This proposal focuses on the role of maternal dietary protein and salt on progeny susceptibility to cardiovascular injury induced by renal ablation. The overall hypothesis postulates that the variability to renal injury and uremic death in an individual could be modified by the levels of maternal dietary protein and salt during perinatal life. Specifically, maternal environment changes the intrinsic characteristics of the offspring kidney by affecting, among other things, early blood pressure and renal development. After weaning, offspring on normal diets maintain normal blood pressure and renal function. However, this is achieved by adaptive mechanisms that alter renal reserve.Therefore, the kidney's response to injury and stress (decrease in renal mass, diabetes, diets, toxics, inflammation etc.) result in diverse blood pressure and renal patterns of damage. The capacity of the glomerulus to increase filtration by enlarging filtering surface area is pivotal for the maintenance of filtration without glomerular hypertension. It is postulated that this capacity is modified by maternal environment. This hypothesis will be tested in Sprague-Dawley rats by using a balanced multifactorial randomized design and statistically assessed by multivariate analysis techniques. The dietary factors will be protein (low; 11% high: 40% and normal: 23%) and NaCl (low: 0.3%, high:4% and normal:0.6%) to be given to the mother during pre-pregnancy, pregnancy, and lactation in 9 protein-salt dietary combinations. After weaning pups will receive a normal diet. At eight weeks of age when pups are sexually mature, pups will be randomly assigned to have 1-2/3 nephrectomies or sham operations (18 groups). Offspring will be monitored to determine morbidity (blood pressure, proteinuria, renal structure) and mortality. Subset of offspring will be randomly allocated for studies to be done as sucklings (day 0-1,7 and 19) and at postweaning age (70 days). The blood pressure response to maternal dietary manipulation and renal ablation will be continuously monitored using telemetry technology from renal ablation to death. Renal reserve will be tested by acute protein load. Filtration surface will be determined by single nephron studies. The critical end points to test the hypothesis will be: 1) glomerular maturation, number, tabular and vascular mass in sucklings, 2) glomerular number, tubular, vascular mass and histopathology of shams and remnant kidneys, 3) total blood pressure response in mmHg/entire period of renal ablation, 4) proteinuria, whole kidney function, and reserve in weanling and mature offspring and 5) glomerular hemodynamics in sham and remnant kidneys. If proven, this work will help the understanding of the variability in hypertension and renal damage in renal disease, establish rationale for preventive measurements, and most important, this work will emphasize the role of maternal nutrition as an essential factor in the health of society.

描述（主要研究者摘要）：一些人群 低蛋白高盐饮食显示终末期肾病的发生率高， 由于肾小球肾炎、糖尿病和高血压导致的衰竭。 这 建议的重点是产妇膳食蛋白质和盐的作用， 后代对肾消融诱导的心血管损伤的易感性。 总体假设假定肾损伤的变异性和 个体的尿毒症死亡可以通过母体的水平来改变， 饮食中的蛋白质和盐。 具体来说，产妇 环境改变了后代肾脏的内在特征 通过影响早期血压和肾功能 发展 断奶后，正常饮食的后代保持正常的 血压和肾功能。 然而，这是通过自适应 因此，肾脏对肾脏的反应， 损伤和压力（肾质量减少，糖尿病，饮食，毒物， 炎症等）导致不同的血压和肾脏模式， 损害 肾小球通过扩大来增加滤过的能力 过滤表面积对于维持过滤是关键的， 肾小球高血压 据推测，这种能力是修改 受到母亲环境的影响。 该假设将在Sprague-Dawley大鼠中通过使用平衡 多因素随机设计，并通过多变量进行统计学评估 分析技术。 饮食因素将是蛋白质（低; 11%高： 40%和正常：23%）和NaCl（低：0.3%，高：4%和正常：0.6%） 在怀孕前，怀孕和哺乳期间给予母亲9 蛋白质-盐饮食组合。 断奶后，幼崽将接受 正常饮食。 在八周大的时候，当幼崽性成熟时， 将被随机分配接受1-2/3肾切除术或假手术 (18组）。 将监测后代以确定发病率（血液 血压、蛋白尿、肾结构）和死亡率。子代子集 将随机分配至研究中，作为哺乳动物（第0- 1天，第7天 和19）和断奶后（70日龄）。 血压反应 母亲的饮食控制和肾脏消融将持续 使用遥测技术监测从肾消融到死亡的整个过程。 肾 储备将通过急性蛋白负荷进行测试。 过滤表面将 通过单肾单位研究确定。 关键终点测试 假设将是：1）肾小球成熟，数量，表格和血管 2）肾小球数量、肾小管、血管质量和 假肾和残肾的组织病理学，3）总血压 反应（mmHg/整个肾消融期），4）蛋白尿，整体 断奶和成熟后代的肾功能和储备，以及5） 假肾和残肾的肾小球血流动力学。 如果被证实，这项工作 将有助于了解高血压和肾功能不全的变异性， 肾脏疾病的损害，建立预防措施的基本原理， 最重要的是，这项工作将强调产妇营养的作用， 作为社会健康的重要因素。