Thurston J H, Hauhart R E, Schulz D W, Naccarato E F, Dodson W E, Carroll J E
Neurology. 1981 Sep;31(9):1063-9. doi: 10.1212/wnl.31.9.1063.
Infant mice (2 to 4 days old) received valproate (100 or 200 mg per kilogram body weight) subcutaneously once daily for 5 days. Both dosages decreased plasma beta-hydroxybutyrate levels to about one-third of the control value, in the face of normal free fatty acid and glycerol levels. At 200 mg per kilogram of valproate, there were significant decreases in brain weight and brain K content. Both doses produced metabolite changes in brain compatible with a reduced metabolic flux through the glycolytic pathway and the citric acid cycle. Valproate reduced brain aspartate but did not increase brain GABA levels in infant mice. At 200 mg per kilogram of valproate, brain glutamate decreased and taurine levels increased. Two hundred milligrams per kilogram of valproate caused a profound reduction of liver glycogen stores. The apparent decrease in cerebral metabolic rate, reduced glutamate and aspartate, and increased levels of taurine in brain may relate to the anticonvulsant action of valproate. Together with the decreased brain weight and K content, the findings are also compatible with maturational delay. Decreased ketonemia and liver glycogen content may relate to the hepatic toxicity associated with valproate administration in infants and children.
对2至4日龄的幼鼠，每天皮下注射丙戊酸盐（每千克体重100或200毫克），持续5天。尽管游离脂肪酸和甘油水平正常，但两种剂量均使血浆β-羟基丁酸水平降至对照值的约三分之一。丙戊酸盐剂量为每千克200毫克时，脑重量和脑钾含量显著降低。两种剂量均使脑内代谢产物发生变化，这与糖酵解途径和柠檬酸循环中代谢通量降低相一致。丙戊酸盐降低了幼鼠脑内天冬氨酸水平，但未提高脑内γ-氨基丁酸水平。丙戊酸盐剂量为每千克200毫克时，脑内谷氨酸水平降低，牛磺酸水平升高。每千克200毫克的丙戊酸盐使肝糖原储备大幅减少。脑代谢率明显降低、谷氨酸和天冬氨酸减少以及脑内牛磺酸水平升高，可能与丙戊酸盐的抗惊厥作用有关。连同脑重量和钾含量降低，这些发现也与发育延迟相符。酮血症降低和肝糖原含量减少可能与婴儿和儿童丙戊酸盐给药相关的肝毒性有关。
