CORE--LABORATORY OF INTEGRATED KIDNEY FUNCTION

核心--综合肾功能实验室

• 批准号: 6725906
• 负责人: Tong Wang Wang
• 金额: $ 17.3万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6725906
• 关键词: biological models; biomedical facility; clearance rate; electrolyte balance; genetically modified animals; kidney function; laboratory mouse; laboratory rat; membrane transport proteins; perfusion; renal tubular transport

Recently, the use of genetically altered animal models became an important tool to examine the contributions of individual channels, transporters and proteins to the maintenance of physiological function and pathophysiology of disease. We are now able to perform renal clearances and in vivo and in vitro tubular microperfusion studies in mice. These techniques will be used to gain insight into the physiological role of specific transporter proteins to tubule and overall renal function. To facilitate the goal of the Program Project to extend our fundamental knowledge about cellular and molecular mechanisms regulating renal tubular function in normal and diseased states, we propose to continue the Small Animal Physiology Core, with the following specific aims: (1) Provide a variety of rat and mouse animal models, such as adrenalectomy and hormone replacement, metabolic or respiratory acidosis and chronic diuretic treatment (furosemide, thiazide). (2) Provide a metabolic measurement of plasma and urine electrolytes and examine the dietary modulations in different animal models, including knockout and mutant mice provided by each PI. (3) Perform renal clearance experiments in rats and mice to examine renal phenotypes in mutant animals and to assess the physiological roles of ion channels, proteins and transporters, such as ENaC, ROMK, CFTR and NKCC2. (4) Measure arterial blood pH, pCO2 and HCO3- and urine pH and HCO3- to evaluate the acid-base status in these animals. (5) Perform in situ microperfusion of the proximal tubule and loop of Henle of rat and mouse to assess segmental tubular function and measure electrolyte content of nanoliter sized samples (Na+, K+, Cl-, total CO2, Ca2+ and Mg2+) of tubular fluid collected from these different sites. (6) Perform in vitro microperfusion of isolated proximal tubule and collecting tubule to examine the electrolyte transport in these segments. (7) Measure tubular absorption of proteins such as albumin to investigate endocytosis-related tubular functions. This core will be utilized by most of the PPG projects.

最近，遗传改变的动物模型成为研究单个通道，转运蛋白和蛋白质对维持生理功能和疾病病理生理学的贡献的重要工具。现在，我们能够在小鼠中进行肾脏清除，体内和体外管状微灌注研究。这些技术将用于深入了解特定转运蛋白在小管和整体肾功能方面的生理作用。 To facilitate the goal of the Program Project to extend our fundamental knowledge about cellular and molecular mechanisms regulating renal tubular function in normal and diseased states, we propose to continue the Small Animal Physiology Core, with the following specific aims: (1) Provide a variety of rat and mouse animal models, such as adrenalectomy and hormone replacement, metabolic or respiratory acidosis and chronic diuretic treatment (furosemide,噻嗪类）。 （2）提供血浆和尿液的代谢测量 电解质并检查不同动物模型中的饮食调制，包括每个PI提供的敲除和突变小鼠。 （3）在大鼠和小鼠中进行肾脏清除实验，以检查突变动物中的肾脏表型，并评估离子通道，蛋白质和转运蛋白的生理作用，例如ENAC，ROMK，CFTR和NKCC2。 （4）测量动脉血液pH，PCO2和HCO3-和尿液pH和HCO3-以评估这些动物的酸碱状态。 （5）进行近端小管和亨勒环的原位微灌注 大鼠和小鼠评估从这些不同位点收集的管状流体的纳米尺寸样品（Na+，K+，Cl-，总CO2，Ca2+和Mg2+）的分段管函数并测量的电解质含量。 （6）对分离的近端小管和收集小管进行体外微灌注，以检查这些段中的电解质转运。 （7）测量蛋白质（例如白蛋白）的管状吸收研究与内吞作用相关的管状功能。大多数PPG项目都将使用该核心。