Department of Medicine V (Hepatology & Gastroenterology), Aarhus University Hospital, Aarhus C, Denmark.
Scand J Clin Lab Invest. 2010 Apr 19;70(3):151-7. doi: 10.3109/00365511003599537.
Catabolism is a serious problem in patients with active inflammation. The tissue nitrogen (N) depletion is related to increased hepatic capacity for elimination of N via conversion of amino-N into urea-N. This is caused by the inflammatory process, but the mediators responsible are unknown. Tumor necrosis factor-alpha (TNF-alpha) plays a key role in inflammation, and we hypothesized that TNF-alpha up-regulates urea synthesis.
We examined the in vivo capacity of urea-N synthesis (CUNS) and mRNA levels of urea cycle enzyme genes 3 h after TNF-alpha injection in rats. Circulating concentrations of glucagon, corticosterone, insulin, glucose, cytokines and acute phase proteins and their liver tissue gene expressions were measured.
TNF-alpha increased CUNS by 40% (p=0.03) despite decreased urea-cycle enzyme gene expression. TNF-alpha increased interleukin 6 (IL-6) (p < 0.001); circulating acute phase proteins were unchanged.
TNF-alpha in rats caused an acute up-regulation of the in vivo capacity of urea synthesis which may promote loss of nitrogen from the body and catabolism. The results indicate that TNF-alpha has a post-transcriptional effect on regulation of urea synthesis that is independent of the acute phase protein synthesis. Effects of IL-6 may be involved.
在有炎症活动的患者中，分解代谢是一个严重的问题。组织氮（N）耗竭与通过将氨基酸 N 转化为尿素 N 增加肝脏消除 N 的能力有关。这是由炎症过程引起的，但负责的介质尚不清楚。肿瘤坏死因子-α（TNF-α）在炎症中起关键作用，我们假设 TNF-α上调尿素合成。
我们检查了 TNF-α 注射后 3 小时大鼠体内尿素-N 合成（CUNS）的能力和尿素循环酶基因的 mRNA 水平。测量了循环中的胰高血糖素、皮质酮、胰岛素、葡萄糖、细胞因子和急性期蛋白及其肝组织基因表达。
TNF-α尽管降低了尿素循环酶基因表达，但仍使 CUNS 增加了 40%（p=0.03）。TNF-α增加了白细胞介素 6（IL-6）（p<0.001）；循环急性期蛋白不变。
大鼠 TNF-α引起体内尿素合成能力的急性上调，这可能导致氮从体内流失和分解代谢。结果表明，TNF-α对尿素合成的调节具有转录后效应，与急性期蛋白合成无关。IL-6 的作用可能涉及其中。
