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，使用基因改变的动物模型成为一个重要的工具，检查个人的通道，转运蛋白和蛋白质的生理功能和疾病的病理生理学的维护的贡献。我们现在能够在小鼠中进行肾清除率和体内及体外肾小管微灌注研究。这些技术将用于深入了解特定转运蛋白对肾小管和整体肾功能的生理作用。为了促进该计划项目的目标，以扩大我们对正常和疾病状态下调节肾小管功能的细胞和分子机制的基本知识，我们建议继续小动物生理学核心，具体目标如下：（1）提供多种大鼠和小鼠动物模型，如肾上腺切除和激素替代、代谢性或呼吸性酸中毒和慢性利尿剂治疗等（呋塞米、噻嗪）。(2)提供血浆和尿液的代谢测量 电解质和检查不同动物模型中的饮食调节，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，以检查突变动物的肾脏表型，并评估离子通道、蛋白质和转运蛋白（如ENaC、ROMK、CFTR和NKCC 2）的生理作用。(4)测量动脉血pH、pCO 2和HCO 3-以及尿液pH和HCO 3-，以评价这些动物的酸碱状态。(5)对近端肾小管和Henle袢进行原位微灌注， 大鼠和小鼠来评估节段性肾小管功能并测量从这些不同部位收集的肾小管液的纳升大小的样品（Na+、K+、Cl-、总CO2、Ca 2+和Mg 2+）的电解质含量。(6)采用离体近端小管和集合小管微灌流法，观察电解质在这些节段中的转运。(7)测量肾小管对蛋白质（如白蛋白）的吸收，以研究内吞相关的肾小管功能。这一核心资源将用于项目编制补助金的大多数项目。