LIVER OXYGENATION AND METABOLIC ZONATION

有人提出，肝脏在代谢上是沿着 循环的长度。在这个概念的极端形式中，在 血液(氧气和底物丰富)进入肝脏的区域， 门静脉周围区，肝脏合成葡萄糖，而在门静脉周围区域 血液(氧气和底物较差)离开肝脏时， 静脉周围带，肝脏分解葡萄糖。整个过程一直是 称为细胞间无效循环，因为一条主要的代谢途径是 在同一器官内以相反的方向运行的。我们的目标是 测试在活体(活体动物)中是否真的存在这种带状组织 因为之前关于这一概念的证据完全来自体外 研究，只能被认为是提示性和高度投机性的。 使用放射性示踪剂标记体内的肝糖原，然后我们将 随后从分离的不同区域分离和分析糖原 肝脏，这将使我们能够表征代谢的程度 肝脏的带状组织。因为很多肝脏的体外证据 分区可能取决于通过肝脏的氧气梯度，我们还将 体内活性生物合成途径的氧依赖性分析 肝细胞和灌流的肝脏系统。各种类型的肝脏缺氧 病理状态可导致细胞损伤和最终死亡，以及 肝脏对新生缺氧的适应，通过减缓生物合成，可以 是一种防止缺氧达到过低水平的机制 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.