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精氨酸对大鼠氨中毒的保护机制。

Mechanism of arginine protection against ammonia intoxication in the rat.

作者信息

Goodman M W, Zieve L, Konstantinides F N, Cerra F B

出版信息

Am J Physiol. 1984 Sep;247(3 Pt 1):G290-5. doi: 10.1152/ajpgi.1984.247.3.G290.

DOI:10.1152/ajpgi.1984.247.3.G290
PMID:6476119
Abstract

To examine the beneficial effect of arginine on ammonia intoxication, rats were injected intraperitoneally with a single dose of NH4Cl (6.75 mmol/kg) with and without arginine (5.0 mmol/kg) or ornithine (5.0 mmol/kg). Arginine or ornithine reduced the blood ammonia nitrogen at 30 min after NH4Cl injection from 3,288 +/- 800 micrograms/dl (mean +/- SE) to 538 +/- 90 and 575 +/- 34 micrograms/dl, respectively. In rats administered this dose of NH4Cl, arginine or ornithine did not increase further the hepatic carbamoyl-phosphate synthetase (EC 6.3.4.16) activation by N-acetylglutamate beyond the effect of NH4Cl. However, arginine or ornithine did increase the hepatic citrulline and urea content as well as the plasma urea concentration in these NH4Cl-injected rats. In rats injected with four doses of NH4Cl (2.5 mmol/kg), arginine or ornithine pretreatment increased the urea excretion and normalized the orotic acid excretion. These results indicate that arginine mitigates ammonia intoxication in the rat by increasing ornithine carbamoyltransferase activity through increased ornithine availability and not via activation of N-acetylglutamate synthetase. By increasing ornithine carbamoyltransferase activity, ornithine enhances the conversion of ammonia to citrulline and urea.

摘要

为研究精氨酸对氨中毒的有益作用,给大鼠腹腔注射单剂量的NH4Cl(6.75 mmol/kg),分别同时给予或不给予精氨酸(5.0 mmol/kg)或鸟氨酸(5.0 mmol/kg)。精氨酸或鸟氨酸使注射NH4Cl后30分钟时的血氨氮从3288±800微克/分升(平均值±标准误)分别降至538±90和575±34微克/分升。在给予该剂量NH4Cl的大鼠中,精氨酸或鸟氨酸并未在NH4Cl的作用基础上进一步增强N - 乙酰谷氨酸对肝氨甲酰磷酸合成酶(EC 6.3.4.16)的激活作用。然而,精氨酸或鸟氨酸确实增加了这些注射NH4Cl大鼠的肝瓜氨酸和尿素含量以及血浆尿素浓度。在注射四剂NH4Cl(2.5 mmol/kg)的大鼠中,精氨酸或鸟氨酸预处理增加了尿素排泄并使乳清酸排泄正常化。这些结果表明,精氨酸通过增加鸟氨酸的可利用性从而增加鸟氨酸氨甲酰转移酶活性,而非通过激活N - 乙酰谷氨酸合成酶来减轻大鼠的氨中毒。通过增加鸟氨酸氨甲酰转移酶活性,鸟氨酸增强了氨向瓜氨酸和尿素的转化。

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