MATERNAL DIET AND PROGENY RENAL INJURY

母亲饮食与后代肾损伤

• 批准号: 3327828
• 负责人: Silvia H Azar
• 金额: $ 14.34万
• 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/3327828
• 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（主要研究者的摘要）：一些人群摄入 低蛋白高盐饮食显示终末期肾病的高发病率 肾小球肾炎、糖尿病和高血压导致的衰竭。 这 该提案的重点是母亲膳食蛋白质和盐对健康的影响 后代对肾脏消融引起的心血管损伤的易感性。 总体假设假设肾损伤和肾损伤的变异性 个体的尿毒症死亡可以通过母体水平来改变 围产期饮食中的蛋白质和盐。 具体来说，产妇 环境改变子代肾脏的内在特征 除其他外，通过影响早期血压和肾脏 发展。 断奶后，正常饮食的后代保持正常 血压和肾功能。 然而，这是通过自适应实现的 改变肾脏储备的机制。因此，肾脏对 损伤和压力（肾质量减少、糖尿病、饮食、有毒物质、 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至关重要，无需 肾小球高血压。 假设这个容量被修改了 受母体环境影响。 该假设将通过使用平衡模型在 Sprague-Dawley 大鼠中进行测试 多因素随机设计和多变量统计评估 分析技术。 饮食因素是蛋白质（低；高 11%： 40%，正常：23%）和 NaCl（低：0.3%，高：4%，正常：0.6%） 9、在怀孕前、怀孕期和哺乳期给予母亲 蛋白质-盐饮食组合。 断奶后，幼犬将收到 正常饮食。 八周大时，幼犬性成熟， 将被随机分配进行 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、肾脏结构）和死亡率。后代的子集 将被随机分配用于以哺乳期进行的研究（第 0-1,7 天） 和 19) 以及断奶后年龄 (70 天)。 血压反应 产妇饮食控制和肾脏消融将持续进行 使用遥测技术监测从肾脏消融到死亡的整个过程。 肾 储备将通过急性蛋白质负荷进行测试。 过滤表面将 由单个肾单位研究确定。 测试的关键终点 假设是： 1) 肾小球成熟度、数量、管状和血管 乳仔质量，2) 肾小球数量、肾小管、血管质量和 假手术和残肾的组织病理学，3) 总血压 mmHg/整个肾脏消融期间的反应，4) 蛋白尿，整体 肾功能，以及断奶和成熟后代的储备和5) 假肾和残肾中的肾小球血流动力学。 如果得到证实，这项工作 将有助于了解高血压和肾病的变异性 肾脏疾病损害，建立预防措施的基本原理， 最重要的是，这项工作将强调孕产妇营养的作用 作为社会健康的一个重要因素。