ALCOHOL-OXYGEN TENSION INTERACTIONS IN LIVER

肝脏中的酒精-氧张力相互作用

• 批准号: 3112860
• 负责人: CAROL C CUNNINGHAM
• 金额: $ 10.39万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-28 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3112860
• 关键词: alcoholic beverage consumption; bioenergetics; drug interactions; high energy compound; laboratory rat; liver; liver ischemia /hypoxia; liver metabolism; methanol poisoning; nuclear magnetic resonance spectroscopy; oxygen consumption; oxygen microelectrode; oxygen tension; perfusion; alcoholic beverage consumption; bioenergetics; drug interactions; high energy compound; laboratory rat; liver; liver ischemia /hypoxia; liver metabolism; methanol poisoning; nuclear magnetic resonance spectroscopy; oxygen consumption; oxygen microelectrode; oxygen tension; perfusion

A major question in the area of ethanol-induced liver damage relates to the role of oxygen deprivation in compromising the viability of the tissue. Previous studies from our laboratory suggest that hepatocytes from ethanol-fed animals cannot maintain an adequate energy state when oxygen deficient. In the present study we will determine whether chronic ethanol consumption makes the intact liver more susceptible to hypoxic damage. A powerful approach to this problem is to monitor the levels of hepatic energy metabolites using 31P-NMR spectroscopy while varying the oxygen tension of the perfusate entering an isolated liver. Experiments are proposed to systematically investigate the effects of hypoxia, acute doses of ethanol, and combinations of the two, on the energy state of perfused livers from both ethanol-fed and control animals. The utilization of oxygen by the liver under all the conditions imposed will be determined by continuous measurements of influent and effluent oxygen tension using micro oxygen electrodes. The study proposed is unique in that it will allow continuous monitoring of high energy phosphorus metabolites and oxygen utilization in the liver under conditions ere nutrient availability and oxygen tension are stringently controlled. This will allow us to establish the relationships between oxygen tension, ethanol metabolism, oxygen utilization and energy state in livers of animals that are chronic ethanol consumers. This study is relevant to the human condition where it has been demonstrated in alcoholics with hepatic necrosis that there can be reductions in hepatic venous oxygen tension.

乙醇引起的肝损伤领域的一个主要问题与 氧气剥夺在损害组织的生存力中的作用。 我们实验室的先前研究表明， 氧气时乙醇喂养的动物无法保持足够的能量状态 不足。在本研究中，我们将确定是否慢性乙醇 消费使完整的肝脏更容易受到低氧损害的影响。一个 解决这个问题的强大方法是监视肝的水平 使用31p-nmr光谱的能量代谢物，同时改变氧气 进入孤立肝脏的灌注张力。实验是 提议系统地研究缺氧，急性剂量的影响 乙醇和两者的组合，以灌注的能量状态 来自乙醇喂养和对照动物的肝脏。利用氧气 在所有施加条件下的肝脏将由肝脏取决于 使用微观对进水氧张力进行连续测量 氧电极。 提出的研究是独一无二的，因为它将允许对 肝脏中高能磷代谢物和氧气利用 在条件下，营养物的可用性和氧气张力是 严格控制。这将使我们能够建立关系 氧张力，乙醇代谢，氧气利用和能量之间 慢性乙醇消费者的动物肝脏中的状态。这项研究 与已证明的人类状况有关 肝坏死的酒精中毒可能会减少肝 静脉氧张力。