LIVER OXYGENATION AND METABOLIC ZONATION

有人提出，肝脏是沿着 循环的长度。 在这个概念的极端形式中， 血液（富含氧气和基质）进入肝脏的区域， 在门静脉周围区，肝脏合成葡萄糖，而在该区域， 血液（氧气和基质更差）离开肝脏， 在静脉周围区，肝脏分解葡萄糖。 整个过程 称为细胞间无效循环，因为一个主要的代谢途径是 在同一个器官中以相反的方向运作。 我们的目标是 测试这种分区是否实际存在于体内（在活动物中） 由于先前关于这一概念的证据仅来自体外 研究，并可以被认为只是暗示性和高度投机性。 使用放射性示踪剂标记体内肝糖原，我们将 随后分离并分析来自分离区域的糖原， 肝脏，这将使我们能够描述代谢的程度， 肝脏的分区。 因为许多体外证据表明肝脏 分区可能取决于通过肝脏的氧梯度，我们还将 分析在生物合成途径中的氧依赖性， 肝细胞和灌注肝系统。 肝脏缺氧 病理状态可能导致细胞损伤并最终死亡，并且 肝脏通过减缓生物合成来适应新生缺氧， 是一种机制，通过这种机制， 在肝脏的流出区。

It has been proposed that the liver is metabolically zonated along the length of the circulation. In the extreme form of this concept, in the region where blood (oxygen and substrate rich) enters the liver, the periportal zone, the liver synthesizes glucose, while in the region from which the blood (oxygen and substrate poorer) leaves the liver, the perivenous zone, the liver breaks down glucose. The whole process has been termed intercellular futile cycling, since a major metabolic pathway is operating in opposing directions within the same organ. Our goal is to test whether such zonation actually exists in vivo (in the live animal) since previous evidence for this concept comes solely from in vitro studies, and can be considered only suggestive and highly speculative. Using radioactive tracers to label liver glycogen in vivo, we will then subsequently isolate and analyze the glycogen from the separate zones of the liver, which will allow us to characterize the degree of metabolic zonation of the liver. Since much of the in vitro evidence for liver zonation may depend on the oxygen gradient through the liver, we will also analyze the oxygen dependence of the actively biosynthetic pathways in hepatocyte and perfused liver systems. Liver hypoxia in various pathological states can lead to cellular damage and eventual death, and adaptation of the liver to nascent hypoxia, by slowing biosynthesis, can be a mechanism by which the hypoxia is kept from reaching too low a level in the effluent regions of the liver.