Basile A S, Saito K, al-Mardini H, Record C O, Hughes R D, Harrison P, Williams R, Li Y, Heyes M P
Laboratory of Neuroscience, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Gastroenterology. 1995 Mar;108(3):818-23. doi: 10.1016/0016-5085(95)90456-5.
BACKGROUND/AIMS: Quinolinic acid is an endogenous neuroexcitant derived from tryptophan. Brain quinolinic acid concentrations are reportedly elevated in chronic liver failure. The aim of this study was to determine if brain quinolinic acid levels correlate with the severity of hepatic encephalopathy.
Postmortem samples of selected brain regions and plasma samples taken at several stages of encephalopathy were obtained from patients with acute and chronic liver failure. Quinolinic acid levels were measured by mass spectroscopy using [18O]quinolinic acid.
Plasma quinolinic acid levels were significantly increased by stage I encephalopathy in patients with acute liver failure and by stages II and III in patients with chronic liver failure. Brain quinolinic acid levels were elevated only in patients with acute liver failure and were uniformly distributed at concentrations below those observed in plasma.
The uniform distribution of quinolinic acid at subplasma concentrations in the brains of patients with acute liver failure suggests that it is synthesized peripherally and enters the brain across a permeabilized blood-brain barrier. Whereas the elevation of brain quinolinic acid levels in patients who died of acute but not chronic liver failure suggests that the involvement of quinolinic acid in the pathogenesis of hepatic encephalopathy is minimal, it could predispose these patients to seizures.
背景/目的：喹啉酸是一种源自色氨酸的内源性神经兴奋性物质。据报道，慢性肝衰竭患者脑内喹啉酸浓度会升高。本研究的目的是确定脑内喹啉酸水平是否与肝性脑病的严重程度相关。
从急性和慢性肝衰竭患者处获取在脑病几个阶段采集的选定脑区的尸检样本和血浆样本。使用[18O]喹啉酸通过质谱法测量喹啉酸水平。
急性肝衰竭患者在I期肝性脑病时血浆喹啉酸水平显著升高，慢性肝衰竭患者在II期和III期时升高。仅急性肝衰竭患者脑内喹啉酸水平升高，且其浓度均匀分布，低于血浆中观察到的浓度。
急性肝衰竭患者脑内喹啉酸在低于血浆浓度时均匀分布，这表明它是在周围合成并通过通透性增加的血脑屏障进入大脑。而死于急性而非慢性肝衰竭患者脑内喹啉酸水平升高表明，喹啉酸在肝性脑病发病机制中的作用极小，但可能使这些患者易患癫痫。
