EFFECTS OF ALCOHOL ON IRON HOMEOSTASIS

酒精中毒和酒精性肝病通常与 铁稳态紊乱，从缺铁性贫血到 血色素沉着症和铁质沉着症。因为肝脏不仅是 铁的储存，但也合成转铁蛋白，主要的血浆铁 转运蛋白，任何肝功能障碍，如由酒精引起的 可能会导致这个器官中铁代谢的戏剧性变化。它是 因此，本项目的主要目的是评估 酒精对大鼠肝脏铁稳态以及其他因素的影响 作为循环内毒素(在酒精性肝病中增加)。 因为脂肪酸与铁的运输和脂肪酸有关 酒精会干扰新陈代谢，这也是检查的次要目标 它们在酒精引起的铁代谢改变中所起的作用 实现这些目标，将实现以下目标：(1) 将检查肝细胞和库普弗细胞的铁负荷或铁耗竭。 从体内和体外的酒精率。转铁蛋白铁摄取，铁蛋白 合成、细胞铁动员与转铁蛋白受体 回收的浓度和回收率将被量化。(2)蜂窝 在这些动物中转铁蛋白受体的控制将是 调查过了。信使和蛋白质合成的速度将是 可测量的，就像退化一样。这个系统将与那个系统进行比较。 去唾液酸糖蛋白与转铁蛋白和转铁蛋白的合成与分泌 铁蛋白。(3)内毒素对酒精中铁代谢的影响 将使用上述系统对老鼠进行进一步分析。长期的 诱导抗体滴度对内毒素的影响 还将接受检查。(4)脂肪酸摄取与铁的关系 将评估急性和慢性酒精中毒大鼠的新陈代谢。两个肠子 和肝脏摄取将使用十二指肠环，分离的细胞和 膜泡。 预计对人类疾病状态的推断将是 极大地促进了这些研究，并将导致更好的 对人体铁代谢紊乱的认识 酗酒者和酒精性肝病。

Alcoholism and alcoholic liver disease are often associated with disturbances to iron homeostasis, ranging from iron deficiency anemia to hemochromatosis and siderosis. Since the liver is not only a major site of iron storage, but also synthesizes transferrin, the major plasma iron transport protein, any hepatic dysfunction, such as that caused by alcohol may result in dramatic alterations to iron metabolism in this organ. It is therefore the primary aim of this project to assess the influence of alcohol on liver iron homeostasis in the rat, as well as other factors such as circulating endotoxins (which are increased in alcoholic liver disease). Since fatty acids have been implicated in iron transport and fatty acid metabolism is disturbed by alcohol, it is also a secondary aim to examine their role in the altered iron metabolism associated with alcohol To achieve these aims, the following goals will be met: (1) The effects of iron loading or depletion will be examined in hepatocytes and Kupffer cells from alcoholic rate in vivo and in vitro. Transferrin iron uptake, ferritin synthesis, cellular iron mobilization and transferrin receptor concentration and rate of recycling will be quantitated. (2) The cellular control of transferrin receptors in these animals will be investigated. The rate of messenger and protein synthesis will be measured, as will degradation. This system will be compared to that for asialoglycoproteins and the synthesis and secretion of transferrin and ferritin. (3) The effects of endotoxins on iron metabolism in alcoholic rats will be analyzed further, using the systems above. The long-term effects of the induction of antibody titers to endotoxins in these rate will also be examined. (4) The relationship of fatty acid uptake to iron metabolism will be assessed in acute and chronic alcoholic rats. Both gut and liver uptake will be analyzed, using duodenal loops, isolated cells and membrane vesicles. It is anticipated that extrapolation to the human disease state will be greatly facilitated by these studies and will lead to a better understanding of the disturbances of iron metabolism that occur in alcoholics and alcoholic liver disease.