慢性肝不全ラットの大脳皮質におけるグルコースの代謝動態—アミノ酸代謝からの検討

GLUCOSE METABOLISM IN RAT CEREBRAL CORTEX IN CHRONIC HEPATIC FAILURE WITH REFERENCE: TO GLUCOSE-DERIVED AMINO ACIDS

　抄録　肝不全脳における代謝異常の解明を意図して，中枢神経系のエネルギー源であるglucoseの代謝動態をアミノ酸代謝の面から検討を試みた。慢性肝不全はWistar系雄ラットに四塩化炭素を投与し作製後，無麻酔下で断頭し，頭頂葉より厚さ0.5mmの100mg切片を得て，酸素で飽和したGey's balanced saltsolution 2.5mlにD-（U-¹⁴C） glucose 0.2μCiを加え37℃で15分間incubateした。この間に産生したCO₂は25％β-phenylethylamineで捕捉し，大脳皮質切片は75％ethanol抽出後に，薄層クロマトグラフィーで二次展開を行いアミノ酸を分離してその放射能活性を測定し，以下の結論を得た。慢性肝不全群では①CO₂産生能は有意に低下した（p＜0.01）。②アミノ酸分画ではglutamateが有意に低下したが（p＜0.01），glutamineは増加傾向（p＜0.10）を，GABAは増加し（P＜0.05），aspartateとalanineには有意差を認めなかった。③全体としてみるとCO₂とglutamateの低下を反映して，glucoseの代謝は有意に低下したが（p＜0.01），一度取り込まれたglucoseはglutamateを介してアンモニア処理機構およびGABAshuntへ積極的に利用されることが明らかにされ，このような病態背景の成立に脳のエネルギー代謝障害が強く関与していることが示唆された。

In order to investigate metabolic derangements in hepatic failure brains, glucose utilization was studied in regard to glucose-derived amino acids. For this purpose, chronic hepatic failure models were produced in adult male Wistar rats by suc-cesive carbontetrachloride injection (0.20 ml/100g, B. W., twice/week) for 13 weeks. They were confirmed to develop chemical chages compatible with hepatic failure, showing markedly elevated serum levels of NH₃, GOT and ALP. Animals were killed by decapitation during fasting and the brains were removed immediately. After the pa-rietal cortical slices were incubated with D-(U-¹⁴C) glucose for 15 min, they were homogenized in 75% ethanol and deproteinized with water saturated chloroform. And the radioactivities of liberated CO₂ and glucose-derived amino acids (glutamate, glutamine, aspartate, alanine and GABA) obtained from the supernatants were measured.

In chronic hepatic failure brains as compared tonormal controls, the amount of radioactivity of the two major metabolites, namely glutamate and CO₂, decreased (p< O.01), but that of aspartate and alanine changed insignificantly, while GABA for-mation increased (p<0.05) and glutamine synthesis tended to increase.

The above results indicate not only that the overall glucose oxidation in chronic hepatic fai-lure brains declines reflecting low production of glutamate and CO₂, but also that glucose-derived glutamate is actively metabolized through GABA shunt and energy-consuming ammonia fixation.