Tamano Haruna, Takeda Atsushi
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
Brain Res Bull. 2004 Sep 30;64(3):273-7. doi: 10.1016/j.brainresbull.2004.07.013.
Glutamate is the major excitatory neurotransmitter in the brain, and the excess of glutamate concentration in the synaptic cleft is a cause of neuronal injury or death. To find out a drug suppressing the excess of extracellular glutamate concentration, the effect of Saiko-ka-ryukotsu-borei-to, a herbal medicine, was examined in the control and zinc-deficient rats, a neurological disease model, by using in vivo microdialysis. The excessive increase in extracellular glutamate in the hippocampus was induced by perfusion with 100 mM KCl for 40 min. Administration of Saiko-ka-ryukotsu-borei-to did not appreciably influence the increase in body weight of the control rats and the retarded increase in body weight of zinc-deficient rats. However, administration of Saiko-ka-ryukotsu-borei-to to the control rats completely suppressed the increase in glutamate concentration in the hippocampal extracellular fluid during stimulation with high K+. The suppressive effect of Saiko-ka-ryukotsu-borei-to was also observed in zinc-deficient rats, in which extracellular glutamate concentration was markedly increased during stimulation with high K+. These results suggest that Saiko-ka-ryukotsu-borei-to is a useful drug for prevention or cure of excitotoxicity of glutamate.
谷氨酸是大脑中主要的兴奋性神经递质，突触间隙中谷氨酸浓度过高是神经元损伤或死亡的一个原因。为了找到一种能抑制细胞外谷氨酸浓度过高的药物，利用体内微透析技术，在对照大鼠和锌缺乏大鼠（一种神经疾病模型）中检测了草药柴胡加龙骨牡蛎汤的效果。通过用100 mM氯化钾灌注40分钟诱导海马体中细胞外谷氨酸过度增加。给予柴胡加龙骨牡蛎汤对对照大鼠体重的增加以及锌缺乏大鼠体重增长迟缓没有明显影响。然而，给对照大鼠服用柴胡加龙骨牡蛎汤完全抑制了高钾刺激期间海马体细胞外液中谷氨酸浓度的增加。在锌缺乏大鼠中也观察到了柴胡加龙骨牡蛎汤的抑制作用，在高钾刺激期间其细胞外谷氨酸浓度明显增加。这些结果表明，柴胡加龙骨牡蛎汤是预防或治疗谷氨酸兴奋性毒性的一种有效药物。
