Tohda Chihiro, Tamura Takayuki, Komatsu Katsuko
Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Brain Res. 2003 Nov 14;990(1-2):141-7. doi: 10.1016/s0006-8993(03)03449-8.
Although Zokumei-to (ZMT), a Kampo formula, has been used for postapopletic sequelae such as paralysis and logopathy, only few studies of this drug have been carried out. We hypothesized that ZMT may affect neuronal plasticity and investigated whether or not this drug is capable of improving learning impairment and synaptic loss observed in patients with Alzheimer's disease (AD). Amyloid beta(25-35) [Abeta(25-35)] (4.7 nmol) was intracerebroventricularly injected into ddY mice (male, 6 weeks old). Fourteen days after the injection, mice were given ZMT extract (500 mg/kg/day) per os for 15 days. In a memory acquisition test, the Abeta(25-35)-injected mice required more time to master this task than did mice in the saline- or reverse peptide Abeta(35-25)-treated groups. ZMT-treated mice shortened escape latencies during trial days 3-5, but not significantly. Three days after the last drug treatment, a retention test was performed. Following ZMT, the number of crossings over a platform was significantly decreased in Abeta(25-35)-injected mice compared with those in the control groups. However, ZMT-treated mice showed complete recovery of this number. Although Abeta(25-35) injection decreased synaptophysin expression in the cerebral cortex and the hippocampus, ZMT treatment significantly increased the level of expression of synaptophysin up to the control level. Donepezil hydrochloride (DNP, 0.5 mg/kg/day, p.o.) clinically used for AD had no effect on memory retention and synaptophysin levels. Abeta(25-35)-induced neuronal loss was not observed in any region of the brain. The present results suggest that memory impairment and synaptic loss in AD patients may be improved by treatment with ZMT, even after such impairment has already progressed.
尽管汉方制剂续命汤（ZMT）已被用于治疗中风后遗症如瘫痪和言语障碍，但对该药物的研究却很少。我们推测ZMT可能会影响神经元可塑性，并研究了这种药物是否能够改善阿尔茨海默病（AD）患者出现的学习障碍和突触丧失。将淀粉样β蛋白（25 - 35）[Aβ（25 - 35）]（4.7 nmol）脑室内注射到ddY小鼠（雄性，6周龄）体内。注射后14天，给小鼠口服ZMT提取物（500 mg/kg/天），持续15天。在记忆获取测试中，注射Aβ（25 - 35）的小鼠比注射生理盐水或反向肽Aβ（35 - 25）的小鼠需要更多时间来掌握这项任务。ZMT处理的小鼠在试验第3 - 5天缩短了逃避潜伏期，但差异不显著。最后一次给药后3天，进行了记忆保持测试。给予ZMT后，与对照组相比，注射Aβ（25 - 35）的小鼠在平台上的穿越次数显著减少。然而，ZMT处理的小鼠该次数完全恢复。尽管注射Aβ（25 - 35）会降低大脑皮质和海马体中突触素的表达，但ZMT处理可使突触素的表达水平显著增加至对照水平。临床上用于治疗AD的盐酸多奈哌齐（DNP，0.5 mg/kg/天，口服）对记忆保持和突触素水平没有影响。在大脑的任何区域均未观察到Aβ（25 - 35）诱导的神经元丢失。目前的结果表明，即使在AD患者的记忆障碍和突触丧失已经进展之后，用ZMT治疗仍可能改善这些症状。
