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HEPATOCYTE VOLUME CONTROL AND ALCOHOLIC INJURY

肝细胞容量控制和酒精损伤

基本信息

批准号：
2044894
负责人：
ROBERT WONDERGEM
金额：
$ 9.38万
依托单位：
EAST TENNESSEE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-06-01 至 1995-05-31
项目状态：
已结题

项目摘要

The long-term goals of this proposal are to elucidate the failure of hepatocyte volume regulation during chronic ethanol ingestion, which results in hepatomegaly. Liver enlargement in turn leads to portal hypertension, impaired microcirculation, and anoxic degeneration of hepatic function. The immediate goal is to determine whether chronic ethanol ingestion in mice or acute administration of ethanol to hepatocytes in primary culture diminishes the capability of liver cells to regulate their volume. The project will utilize a novel, electrophysiological technique to measure change in hepatocyte water volume. The specific aims are 1) to determine the membrane water permeability coefficient for hepatocytes in primary culture and whether it is affected by ethanol; 2) to determine whether hepatocytes in primary monolayer culture regulate their volume in response to perturbations in external osmolality and whether volume regulation diminishes with chronic and acute effects of ethanol; 3) to determine whether rapid volume regulation in cultured hepatocytes facilitates secondary active transport of L-alanine by compensating for the osmolality of accumulated organic solute and whether this diminishes due to ethanol; 4) to determine whether passive, redistribution of cellular Cl- is voltage-driven by osmotically-induced changes in cell transmembrane potential, which constitutes a novel means for control of cell volume. Successful completion of this project will expand our knowledge of the mechanisms of hepatocyte volume regulation. Moreover, the health-relatedness of these studies will be the generation of new information on how chronic and acute effects of ethanol inhibit hepatocyte volume regulation, which in turn results in cell hypertrophy, hepatomegaly, and the sequelae of deteriorated hepatic function.

该提案的长期目标是阐明慢性乙醇摄入期间肝细胞体积调节失败，导致肝肿大肝脏增大又导致门静脉高血压、微循环障碍和缺氧变性，肝功能当前的目标是确定慢性乙醇摄入小鼠或急性给予乙醇，原代培养中的肝细胞降低了肝细胞来调节它们的体积。该项目将利用一本小说，电生理技术测量肝细胞水的变化音量. 具体目的是：1）确定膜水原代培养中肝细胞的渗透系数以及它受乙醇的影响; 2）确定原代肝细胞中单层培养物调节它们体积以响应外部渗透压和容量调节是否随着慢性和乙醇的急性效应; 3）以确定是否快速量培养肝细胞中的调节促进次级主动转运通过补偿积累的有机物的渗透压，溶质，以及是否由于乙醇而减少; 4）确定细胞Cl-的被动再分布是否是由电压驱动的，诱导细胞跨膜电位的变化，构成了控制细胞体积的新手段。成功该项目的完成将扩大我们的知识的机制，肝细胞体积调节此外，这些与健康有关的研究将产生新的信息，乙醇的急性作用抑制肝细胞体积调节，转导致细胞肥大，肝肿大，以及肝功能恶化。