Kikuchi S, Matsumoto H, Yachi A
No To Shinkei. 1984 Sep;36(9):889-93.
The etiology of uremic encephalopathy remains largely unknown. In order to elucidate the role of amino acid changes in uremic encephalopathy, the free amino acids in serum and cerebral cortex were measured in the experimental uremic models. The rats weighing 200 g underwent bilateral ureteral ligation for 48 hours (acute uremia), while the other animals were kept for 4 months after unilateral nephrectomy followed by partial 2/3 nephrectomy of the remaining kidney (chronic uremia). They were confirmed to develop chemical changes compatible with uremia showing markedly elevated serum levels of BUN, creatinine and K+, and were compared with the sham-operated controls. The amino acid patterns, obtained from serum and cerebral cortex, were essentially identical in both acute and chronic uremia. In serum, aspartic acid, glycine and 3-methylhistidine were significantly elevated, and in addition citrulline, alpha-aminoadipic acid, cystine and gamma-aminobutyric acid specifically appeared in uremia. On the contrary, glutamic acid, leucine, lysine, tryptophan, tyrosine and valine were significantly reduced. Tyrosine/phenylalanine ratio, valine/glycine ratio, essential amino acids/non essential amino acids ratio were also apparently reduced in uremia. In cerebral cortex, aspartic acid, glutamine, glycine, histidine, ornithine, phenylalanine, phosphoethanolamine and taurine were significantly elevated, whereas 1-methylhistidine and 3-methylhistidine were specifically detected. Carnocine, glutamic acid and ornithine disclosed a significant reduction in uremia. The above complicated changes in cerebral cortex could not be explained simply by the enhanced permeability of the blood-brain barrier, or by the accelerated ammonia fixation. Therefore, it was suggested that the amino acid levels in cerebral cortex vary under the control of the sophisticated mechanism.
尿毒症性脑病的病因在很大程度上仍然不明。为了阐明氨基酸变化在尿毒症性脑病中的作用，在实验性尿毒症模型中测量了血清和大脑皮层中的游离氨基酸。体重200克的大鼠双侧输尿管结扎48小时（急性尿毒症），而其他动物在单侧肾切除术后保留4个月，然后对剩余肾脏进行2/3部分肾切除（慢性尿毒症）。证实它们出现了与尿毒症相符的化学变化，血清尿素氮、肌酐和钾离子水平显著升高，并与假手术对照组进行了比较。急性和慢性尿毒症中，血清和大脑皮层的氨基酸模式基本相同。血清中，天冬氨酸、甘氨酸和3-甲基组氨酸显著升高，此外瓜氨酸、α-氨基己二酸、胱氨酸和γ-氨基丁酸在尿毒症中特异性出现。相反，谷氨酸、亮氨酸、赖氨酸、色氨酸、酪氨酸和缬氨酸显著降低。尿毒症时酪氨酸/苯丙氨酸比值、缬氨酸/甘氨酸比值、必需氨基酸/非必需氨基酸比值也明显降低。大脑皮层中，天冬氨酸、谷氨酰胺、甘氨酸、组氨酸、鸟氨酸、苯丙氨酸、磷酸乙醇胺和牛磺酸显著升高，而特异性检测到1-甲基组氨酸和3-甲基组氨酸。肌肽、谷氨酸和鸟氨酸在尿毒症时显著降低。大脑皮层中上述复杂变化不能简单地用血脑屏障通透性增强或氨固定加速来解释。因此，有人提出大脑皮层中的氨基酸水平在复杂机制的控制下发生变化。
