EFFECT OF REDUCING BRAIN GLUTAMINE SYNTHESIS ON METABOLIC SYMPTOMS OF HEPATIC-ENCEPHALOPATHY
EFFECT OF REDUCING BRAIN GLUTAMINE SYNTHESIS ON METABOLIC SYMPTOMS OF HEPATIC-ENCEPHALOPATHY
复制标题
DOI：
10.1111/j.1471-4159.1993.tb03247.x
复制
发表时间：
1993-03-01
影响因子：
4.7
通讯作者：
DEJOSEPH, MR
中科院分区：
文献类型：
--
作者：
HAWKINS, RA;JESSY, J;DEJOSEPH, MR
肝功能衰竭，或肠道血液在肝脏周围分流，会导致高氨血症和脑功能障碍。最近有研究表明，氨在脑内被谷氨酰胺合成酶代谢后才引起肝性脑病的一些代谢征象。在本研究中，在大鼠门静脉分流时或3-4周后给予小剂量的蛋氨酸亚砜胺（一种大脑谷氨酰胺合成酶抑制剂）。在注射抑制剂后1-3天测量对门静脉分流产生的几种特征性脑代谢异常的影响。所有未经治疗的门静脉分流大鼠血浆和脑氨浓度升高，脑谷氨酰胺和色氨酸含量增加，脑葡萄糖消耗减少，血脑屏障对色氨酸的通透性增加。所有处理的大鼠氨浓度均较高，但脑内谷氨酰胺含量正常，表明谷氨酰胺合成受到抑制。分流和蛋氨酸亚砜给药后1天，葡萄糖消耗、色氨酸运输和色氨酸脑含量保持在控制值附近。在3-4周分流的大鼠中，在给药后1-3天进行研究，效果不太明显。脑葡萄糖消耗和色氨酸含量部分正常化，但色氨酸运输不受影响。结果与我们早期的结论一致，即谷氨酰胺合成是高氨状态下脑代谢异常发展的重要步骤。
Liver failure, or shunting of intestinal blood around the liver, results in hyperammonemia and cerebral dysfunction. Recently it was shown that ammonia caused some of the metabolic signs of hepatic encephalopathy only after it was metabolized by glutamine synthetase in the brain. In the present study, small doses of methionine sulfoximine, an inhibitor of cerebral glutamine synthetase, were given to rats either at the time of portacaval shunting or 3-4 weeks later. The effects on several characteristic cerebral metabolic abnormalities produced by portacaval shunting were measured 1-3 days after injection of the inhibitor. All untreated portacaval-shunted rats had elevated plasma and brain ammonia concentrations, increased brain glutamine and tryptophan content, decreased brain glucose consumption, and increased permeability of the blood-brain barrier to tryptophan. All treated rats had high ammonia concentrations, but the brain glutamine content was normal, indicating inhibition of glutamine synthesis. One day after shunting and methionine sulfoximine administration, glucose consumption, tryptophan transport, and tryptophan brain content remained near control values. In the 3-4-week-shunted rats, which were studied 1-3 days after methionine sulfoximine administration, the effect was less pronounced. Brain glucose consumption and tryptophan content were partially normalized, but tryptophan transport was unaffected. The results agree with our earlier conclusion that glutamine synthesis is an essential step in the development of cerebral metabolic abnormalities in hyperammonemic states.