癫痫大鼠额叶、海马丙戊酸神经药代动力学的研究

A study of neuropharmacokinetics of VPA in epileptic rat hippocampus and frontal cortex

目的 研究癫痫大鼠额叶、海马的丙戊酸神经药代动力学。方法 健康雄性SD大鼠12只 ,随机分成对照组与癫痫组 ,每组各 6只。癫痫组大鼠用印防己碱腹腔注射点燃 ,腹腔注射丙戊酸钠 40 0mg/kg后不同时间点收集两组大鼠额叶、海马细胞外液透析液及血标本。结果 丙戊酸迅速吸收入脑中 ,在脑中浓度显著低于血中浓度 ;癫痫大鼠与正常大鼠的神经药代动力学参数之间差异无显著性 ,癫痫大鼠额叶、海马浓度 时间曲线下面积差异无显著性 ;给药 1h后额叶、海马丙戊酸浓度与血清丙戊酸浓度均呈下降趋势。结论 癫痫大鼠与正常大鼠额叶、海马丙戊酸神经药代动力学特征相似 ;丙戊酸均匀分布于癫痫大鼠额叶、海马 ,可能与不同脑区脑血流量不同、血脑屏障功能障碍及穿过血脑屏障需单羧酸载体转运等因素有关 ;监测给药

Objective To explore the neuropharmacokinetic character of valproate (VPA) in epileptic rat hippocampus and frontal cortex extracellular fluid(ECF). Methods Twelve healthy male SD rats were divided into a normal group and an epileptic group randomly, with six in each group. Epileptic rats were kindled by picrotoxin intraperitoneal injection. After intraperitoeal injection of VPA 400 mg/kg, ECF samples of frontal cortex and hippocampus and blood samples were collected from both groups at different time points. Results VPA was rapidly uptaken into brain; VPA concentration in rat brain was lower than that in serum. There was no significant difference inneuropharmacokinetic parameters between epileptic rats and normal rats; After the first 60 minute administration, both brain ECF and serum VPA concentration displayed a stable decreasing tendency. Conclusion VPA pharmacokinetic character in epileptic rat brain was similar to that in normal rat brain. VPA was widely distributed in epileptic rat brain. The distribution was related with different amount of blood flow, the damage degree of blood brain barrier and the number of monocarboxylic acid carrier in capillary endothelium of different brain regions. Monitoring of serum VPA concentration time course after a 60 minute administration can indirectly reflect VPA concentration change in brain ECF.