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目的:研究和阐明TAK-147对东莨菪碱诱发的大鼠空间记忆损伤的作用.方法:采用Morris水迷宫的程序研究大鼠的空间记忆,利用开场实验方法测定动物自发活动量.结果:在水迷宫的学习过程中,腹腔内注射东莨菪碱(0.4mg/kg,ip)明显延长大鼠上台的潜伏期,而腹腔内注射TAK-147或donepezil(多奈哌齐)能剂量依赖性地改善东莨菪碱诱发的记忆损伤,两药在0.1-1.0mg/kg的剂量时具有显著性差异.在记忆的再生过程中,腹腔内注射东莨菪碱(1.5mg/kg,ip)引起空间记忆再生过程的障碍分别被TAK-147(0.1,0.3和1.0mg/kg)、多奈哌齐(0.3和1.0mg/kg)以及他克林(3和5mg/kg)显著性改善.TAK-147的作用比多奈哌齐略强却明显强于他克林.此外,在开场实验中,TAK-147和多奈哌齐与生理盐水和东莨菪碱相比,对大鼠运动量未产生明显改变.结论:TAK-147在空间认知功能上起重要的作用,进一步证明TAK-147能够成为一个治疗阿尔采默病的理想的胆碱酯酶抑制药.
OBJECTIVE: To study and elucidate the effect of TAK-147 on scopolamine-induced spatial memory impairment in rats.Methods: Morris water maze program was used to study the spatial memory of rats and the spontaneous activity of animals was measured by open field test.Results: Intraperitoneal injection of scopolamine (0.4 mg / kg, ip) significantly prolonged the latency to go up in rats, whereas intraperitoneal injection of TAK-147 or donepezil dose-dependently improved scopolamine-induced memory impairment. Two There was a significant difference in the dose of 0.1-1.0 mg / kg during the process of memory regeneration, and the barriers of spatial memory regeneration induced by intraperitoneal injection of scopolamine (1.5 mg / kg, ip) were respectively inhibited by TAK-147 (0.1, 0.3 and 1.0 mg / kg), donepezil (0.3 and 1.0 mg / kg), and tacrine (3 and 5 mg / kg) .TAK-147 was slightly more potent than donepezil but significantly stronger than tacrine , TAK-147 and donepezil had no significant changes in physical activity compared with normal saline and scopolamine.Conclusion: TAK-147 plays an important role in spatial cognitive function, which further proves that TAK-147 can Become a cure al Ideal silent disease cholinesterase inhibitor.