Organ Distribution of 13N Following Intravenous Injection of [13N]Ammonia into Portacaval-Shunted Rats.
Organ Distribution of 13N Following Intravenous Injection of [13N]Ammonia into Portacaval-Shunted Rats.
复制标题
门静脉分流大鼠静脉注射[13N]氨后13N的器官分布。
DOI：
10.1007/s11064-016-2096-5
复制
发表时间：
2017
影响因子：
4.4
通讯作者：
Cooper,ArthurJL
中科院分区：
文献类型：
--
作者：
Cruz,NancyF;Dienel,GeraldA;Patrick,PatriciaA;Cooper,ArthurJL
氨具有神经毒性，慢性高氨血症被认为是肝病患者肝性脑病的主要促成因素。大鼠门腔静脉分流被用作动物模型，以研究氨水平升高对身体组织的有害代谢影响，特别是高血氨有害靶向的脑和睾丸。在正常成年大鼠中，与肺、肾、肝和其他一些器官相比，静脉推注[13 N]氨后，这些器官中标记物的初始摄取（表示为相对浓度）相对较低。本研究的目的是确定静脉注射[13 N]氨后，在14个器官中的门腔静脉分流大鼠在分流建设后12周的标签分布。在[13 N]氨给药后的早期时间点（12 s），肺中标记物的相对浓度最高，肾脏和心脏中的相对浓度较低，但仍相当可观。在注射后2-10 min内，门腔静脉分流大鼠血液和肾脏中13 N的清除率比正常大鼠慢。在注射后的后期，大脑和睾丸的13 N水平往往高于正常水平，而两组中许多其他组织的水平相似。因此，肝脏从循环血液中去除氨的减少将更多的氨转移到肝外组织，包括脑和睾丸，并改变这些组织中的氮稳态。这些结果强调了旨在降低肝病患者血氨水平的治疗模式的重要性。
Ammonia is neurotoxic, and chronic hyperammonemia is thought to be a major contributing factor to hepatic encephalopathy in patients with liver disease. Portacaval shunting of rats is used as an animal model to study the detrimental metabolic effects of elevated ammonia levels on body tissues, particularly brain and testes that are deleteriously targeted by high blood ammonia. In normal adult rats, the initial uptake of label (expressed as relative concentration) in these organs was relatively low following a bolus intravenous injection of [13N]ammonia compared with lungs, kidneys, liver, and some other organs. The objective of the present study was to determine the distribution of label following intravenous administration of [13N]ammonia among 14 organs in portacaval-shunted rats at 12 weeks after shunt construction. At an early time point (12 s) following administration of [13N]ammonia the relative concentration of label was highest in lung with lower, but still appreciable relative concentrations in kidney and heart. Clearance of13N from blood and kidney tended to be slower in portacaval-shunted rats versus normal rats during the 2–10 min interval after the injection. At later times post injection, brain and testes tended to have higher-than-normal13N levels, whereas many other tissues had similar levels in both groups. Thus, reduced removal of ammonia from circulating blood by the liver diverts more ammonia to extrahepatic tissues, including brain and testes, and alters the nitrogen homeostasis in these tissues. These results emphasize the importance of treatment paradigms designed to reduce blood ammonia levels in patients with liver disease.