CORE--LABORATORY OF INTEGRATED KIDNEY FUNCTION

近年来，使用转基因动物模型成为研究个体通道、转运体和蛋白质对维持生理功能和疾病病理生理的贡献的重要工具。我们现在能够在小鼠体内和体外进行肾脏清除和小管微灌注研究。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。为了实现本项目的目标，扩展我们对正常和病变状态下调节肾小管功能的细胞和分子机制的基础知识，我们建议继续开展小动物生理学核心，具体目标如下：(1)提供多种大鼠和小鼠动物模型，如肾上腺切除术和激素替代，代谢性或呼吸性酸中毒和慢性利尿剂治疗（速尿，噻嗪）。(2)提供血浆和尿液的代谢测量

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.