MECHANISMS OF BILE FORMATION

这份提案描述了一项基础生理学的研究计划，旨在 阐明肝转运机制及其发病机制 胆汁淤积症。这些实验旨在实现以下目标 目标：1)汇编一个全面的动力学描述 典型有机溶质在实验过程中的迁移动力学 胆汁排泄症和胆汁淤积症，2)探索动力学、特异性和 肝脏有效去除的过程的功能重要性 广泛与血清白蛋白结合的溶质，以及3)构建和 分析胆小管胆汁形成的数学模型，可以提供 对跨小叶浓度决定因素的新见解 小管内的流动情况。实验准备工作包括 分离的灌流大鼠肝脏，灌流的大鼠末端回肠节段，以及 分离大鼠肝细胞。分析方法严重依赖于 隔室分析的生物数学。

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.