MECHANISMS OF BILE FORMATION

该提案描述了一项基础生理学研究计划，旨在 阐明肝转运机制和发病机制， 胆汁淤积 这些实验旨在追求以下目标 目标：1）组装一个全面的动力学描述的 实验过程中代表性有机溶质的迁移动力学 胆汁分泌和胆汁淤积，2）探索动力学，特异性， 肝脏有效清除肝脏内毒素的过程的重要性 与血清白蛋白广泛结合的溶质，和3）构建和 分析小管胆汁形成的数学模型， 对跨小叶浓度决定因素的新认识， 泪小管中的流速分布。 实验准备工作包括 离体灌注的大鼠肝脏，灌注的大鼠末端回肠段，和 分离的大鼠肝细胞。 分析方法严重依赖于 房室分析的生物数学

This proposal describes a research program in basic physiology aimed at elucidating the mechanism of hepatic transport and the pathogenesis of cholestasis. The experiments are designed to pursue the following objectives: 1) assemble a comprehensive kinetic description of the transport kinetics of representative organic solutes during experimental choleresis and cholestasis, 2) explore the kinetics, specificity, and functional importance of the process by which the liver efficiently removes solutes that are extensively bound to serum albumin, and 3) construct and analyze a mathematical model of canalicular bile formation that can provide new insights into the determinants of the translobular concentration and flow profiles in the canaliculi. The experimental preparations include isolated perfused rat livers, perfused segments of rat terminal ileum, and isolated rat hepatocytes. The analytical methods rely heavily on the biomathematics of compartmental analysis.