L-鸟氨酸与L-鸟氨酸-L-天冬氨酸治疗大鼠高氨血症性脑病的比较

L-ornithine vs. L-ornithine-L-aspartate as a treatment for hyperammonemia-induced encephalopathy in rats.

作者信息

Vogels B A, Karlsen O T, Mass M A, Boveé W M, Chamuleau R A

机构信息

University of Amsterdam, Department of Experimental Internal Medicine, The Netherlands.

出版信息

J Hepatol. 1997 Jan;26(1):174-82. doi: 10.1016/s0168-8278(97)80024-4.

DOI:10.1016/s0168-8278(97)80024-4

PMID:9148009

Abstract

BACKGROUND/AIMS: The effect of L-ornithine (ORN) and L-ornithine-L-aspartate (OA) therapy on "extracerebral" nitrogen metabolism, brain metabolism and neurotransmission has been investigated in portacaval shunted rats with hyperammonemia-induced encephalopathy.

METHODS

One day before ammonium-acetate infusion, a portacaval shunt was performed in three experimental groups: 1-control rats, 2-ORN-treated rats and 3-OA-treated rats. Ammonium-acetate was given as an intravenous bolus injection (0.4 mmol.kg bw-1) followed by a constant infusion (1.9 mmol.kg bw-1.h-1) so that steady-state blood ammonia concentrations (500-800 microM) were obtained in the course of 5 h. After 1 h, ammonium-acetate infusion, either L-ornithine or L-ornithine-L-aspartate, was infused for the next 4 h (3.0 mmol.kg bw-1.h-1) in the treated groups. The following parameters were measured: clinical grade of encephalopathy, EEG activity (n = 10 - 20/group), amino acids in plasma (n = 10 - 20/group) and brain dialysate (n = 5 - 9/group), and brain metabolites obtained by in vivo cerebral 1H-MRS (n = 4 - 6/group).

RESULTS

ORN and OA treatment resulted in significantly lower blood (34% and 39%) and brain (42% and 22%) ammonia concentrations, significantly higher urea production (39% and 86%) and significantly smaller increases in brain glutamine and lactate concentrations than in controls. These changes were associated with a significantly smaller increase in clinical grade of encephalopathy in ORN- and OA-treated rats, and a significant improvement in EEG activity in ORN-treated rats. OA-treated rats showed a significant increase in aspartate and glutamate concentrations in brain dialysate.

CONCLUSIONS

The beneficial effects of both treatments on the manifestations of hyperammonemia-induced encephalopathy can be explained by a reduction in blood and brain ammonia concentrations. It is suggested that when OA is administered, the effect of ornithine is partly counteracted by aspartate, inducing high brain extracellular concentrations of the two excitatory amino acids glutamate and aspartate, and perhaps causing overstimulation of NMDA receptors.

摘要

背景/目的：在患有高氨血症性脑病的门腔分流大鼠中，研究了L-鸟氨酸（ORN）和L-鸟氨酸-L-天冬氨酸（OA）疗法对“脑外”氮代谢、脑代谢和神经传递的影响。

方法

在输注醋酸铵前一天，对三个实验组进行门腔分流：1-对照组大鼠，2-ORN治疗组大鼠和3-OA治疗组大鼠。以静脉推注（0.4 mmol·kg体重-1）给予醋酸铵，随后持续输注（1.9 mmol·kg体重-1·h-1），以便在5小时内获得稳态血氨浓度（500 - 800 μM）。在输注醋酸铵1小时后，在治疗组中接下来的4小时内输注L-鸟氨酸或L-鸟氨酸-L-天冬氨酸（3.0 mmol·kg体重-1·h-1）。测量以下参数：脑病临床分级、脑电图活动（每组n = 10 - 20）、血浆氨基酸（每组n = 10 - 20）和脑透析液氨基酸（每组n = 5 - 9），以及通过体内脑1H-MRS获得的脑代谢物（每组n = 4 - 6）。

结果

ORN和OA治疗导致血氨浓度（分别降低34%和39%）和脑氨浓度（分别降低42%和22%）显著降低，尿素生成显著增加（分别增加39%和86%），并且与对照组相比，脑谷氨酰胺和乳酸浓度的增加显著更小。这些变化与ORN和OA治疗组大鼠脑病临床分级的增加显著更小以及ORN治疗组大鼠脑电图活动的显著改善相关。OA治疗组大鼠脑透析液中天冬氨酸和谷氨酸浓度显著增加。