Bergqvist P B, Carpenedo R, Apelqvist G, Moroni F, Bengtsson F
Department of Clinical Pharmacology, Lund University, Sweden.
Pharmacol Toxicol. 1999 Sep;85(3):138-43. doi: 10.1111/j.1600-0773.1999.tb00081.x.
It has previously been shown that the neurodepressant L-tryptophan metabolite oxindole is increased in the blood and brain of rats with fulminant hepatic failure and in the blood of cirrhotic patients affected by chronic hepatic encephalopathy. In the present investigation, we found that oxindole levels were significantly increased in the blood and brain of portacaval-shunted rats, an animal model of chronic hepatic encephalopathy, compared with sham-operated controls. A further increase in plasma and brain oxindole content was found after oral administration of L-tryptophan (300 mg/kg) to both portacaval-shunted or sham-operated animals, while intraperitoneal injection of the amino acid did not modify oxindole content either in brain or blood. Ammonium acetate administration (4.0 mmol/kg, intraperitoneal) reversibly deteriorated the neurological status of portacaval-shunted animals, but did not modify, in a directly related manner, plasma and brain oxindole content. The present findings are in line with the possibility that oxindole may be an additional L-tryptophan-related candidate in the pathogenesis of chronic hepatic encephalopathy.
先前的研究表明，在暴发性肝衰竭大鼠的血液和大脑中，以及在患有慢性肝性脑病的肝硬化患者的血液中，神经抑制剂L-色氨酸代谢产物羟吲哚会增加。在本研究中，我们发现，与假手术对照组相比，作为慢性肝性脑病动物模型的门腔分流大鼠的血液和大脑中羟吲哚水平显著升高。在给门腔分流或假手术动物口服L-色氨酸（300 mg/kg）后，血浆和大脑中的羟吲哚含量进一步增加，而腹腔注射该氨基酸对大脑或血液中的羟吲哚含量均无影响。腹腔注射醋酸铵（4.0 mmol/kg）会使门腔分流动物的神经状态可逆性恶化，但与血浆和大脑中的羟吲哚含量并无直接关联。目前的研究结果符合羟吲哚可能是慢性肝性脑病发病机制中另一种与L-色氨酸相关的候选因素这一可能性。
