Cangiano C, Cardelli-Cangiano P, Cascino A, Ceci F, Fiori A, Mulieri M, Muscaritoli M, Barberini C, Strom R, Rossi Fanelli F
III Department of Internal Medicine, University of Rome La Sapienza, Italy.
J Neurochem. 1988 Dec;51(6):1675-81. doi: 10.1111/j.1471-4159.1988.tb01144.x.
The neurological disorders seen in patients with chronic renal failure and liver cirrhosis are analogous. Previous in vivo studies have shown that the impaired blood-brain amino acid transport seen in rats with chronic renal failure is similar to that of rats with portocaval anastomosis. To elucidate whether a comparable underlying pathogenic mechanism plays a role in both pathological conditions, blood and brain amino acid levels together with amino acid transport by isolated brain microvessels have been studied in rats with chronic renal failure and in sham-operated rats. Brain microvessels isolated from rats with experimental chronic renal failure showed that the uptake of labeled large neutral amino acid, i.e., leucine or phenylalanine, but not of lysine or alpha-methylaminoisobutyric acid, was significantly increased with respect to sham-operated rats; conversely, the uptake of glutamic acid in rats with chronic renal failure was significantly lower compared with values in controls. Kinetic analysis indicated that this was mainly due to increased exchange transport activity (Vmax) of the L-system, rather than to changes in the affinity (Km) of the carrier system for the relative substrate. These data, together with the significant rise of brain glutamine levels and an increased brain-to-plasma ratio of the sum of large neutral amino acids, are analogous to what was previously observed in rats with portocaval anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)
慢性肾衰竭患者和肝硬化患者出现的神经功能障碍具有相似性。以往的体内研究表明，慢性肾衰竭大鼠中出现的血脑氨基酸转运受损情况与门腔静脉吻合大鼠的类似。为了阐明是否有类似的潜在致病机制在这两种病理状况中起作用，研究人员对慢性肾衰竭大鼠和假手术大鼠的血液及脑氨基酸水平以及分离出的脑微血管的氨基酸转运情况进行了研究。从实验性慢性肾衰竭大鼠分离出的脑微血管显示，与假手术大鼠相比，标记的大中性氨基酸（即亮氨酸或苯丙氨酸）的摄取显著增加，但赖氨酸或α-甲基氨基异丁酸的摄取没有增加；相反，慢性肾衰竭大鼠中谷氨酸的摄取与对照组相比显著降低。动力学分析表明，这主要是由于L系统的交换转运活性（Vmax）增加，而非载体系统对相关底物的亲和力（Km）发生变化。这些数据，连同脑谷氨酰胺水平的显著升高以及大中性氨基酸总和的脑血浆比值增加，与之前在门腔静脉吻合大鼠中观察到的情况类似。（摘要截选至250词）
