Knudsen G M, Schmidt J, Almdal T, Paulson O B, Vilstrup H
Department of Neurology, University Hospital, Rigshospitalet, Copenhagen, Denmark.
Hepatology. 1993 Jun;17(6):987-92.
We repeatedly measured blood-brain barrier passage of phenylalanine, leucine, glucose and GABA in nine patients with hepatic encephalopathy using the intravenous double-indicator technique. Controls were four patients without liver disease and two of the patients who had recovered completely from their hepatic encephalopathy. The corrected cerebral venous output curves were fitted by use of a three-compartment model with four parameters. In the patients with hepatic encephalopathy, the permeability-surface area products for phenylalanine and leucine from the blood to the brain and from the brain interstitial fluid to the intracellular compartment, the unidirectional extraction and the brain amino acid influx were similar in the two groups. The permeability from the brain back to blood for phenylalanine was decreased by 72% in patients with hepatic encephalopathy compared with that in the control group (p < 0.05), whereas no difference was seen for leucine. The permeability from the brain back to the blood for phenylalanine decreased with coma grade and normalized in the two patients who recovered. Correspondingly, the calculated brain interstitial fluid concentration of phenylalanine was increased in the patients with hepatic encephalopathy. The transfer variables for blood-brain barrier passage of glucose were similar in the two groups. The permeability from the blood to the brain for GABA was very low in both the patients with hepatic encephalopathy and the control group. We conclude that in hepatic encephalopathy the permeability from brain to blood for phenylalanine decreases with coma grade. The decrease is caused by an increased interstitial fluid concentration of the amino acid. No evidence was found of general or selective blood-brain barrier disturbance in hepatic encephalopathy.
我们采用静脉注射双指示剂技术，对9例肝性脑病患者的苯丙氨酸、亮氨酸、葡萄糖和γ-氨基丁酸的血脑屏障通透性进行了反复测量。对照组为4例无肝脏疾病的患者以及2例已从肝性脑病中完全康复的患者。校正后的脑静脉输出曲线采用具有四个参数的三室模型进行拟合。在肝性脑病患者中，苯丙氨酸和亮氨酸从血液到脑以及从脑间质液到细胞内室的通透表面积乘积、单向摄取和脑氨基酸流入量在两组中相似。与对照组相比，肝性脑病患者中苯丙氨酸从脑回流入血的通透性降低了72%（p < 0.05），而亮氨酸则无差异。苯丙氨酸从脑回流入血的通透性随昏迷程度降低，且在康复的2例患者中恢复正常。相应地，肝性脑病患者中计算得出的脑间质液苯丙氨酸浓度升高。两组中葡萄糖血脑屏障通透的转移变量相似。肝性脑病患者和对照组中γ-氨基丁酸从血液到脑的通透性均非常低。我们得出结论，在肝性脑病中，苯丙氨酸从脑到血的通透性随昏迷程度降低。这种降低是由氨基酸间质液浓度升高所致。未发现肝性脑病存在一般性或选择性血脑屏障紊乱的证据。
