加味开心散对多因素神经损伤痴呆小鼠学习记忆能力的影响
Research of Jiawei Kaixin San on Improving Learning and Memory Abilities of Multiple Neuronal Damage Induced Dementia Mice
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摘要: 目的 研究加味开心散对多因素神经损伤痴呆小鼠学习记忆能力的影响及作用机制。方法 利用多因素神经损伤构建痴呆小鼠模型,给以加味开心散水提物与水醇共提物,以石杉碱甲(0.05mg/kg)作为阳性对照药物,连续灌胃10d;采用Morris水迷宫与主动避暗实验等行为学实验,评价加味开心散对多因素神经损伤痴呆小鼠学习记忆能力的影响。同时测定受试小鼠大脑皮层中胆碱酯酶(ChE)、超氧化物歧化酶(SOD)活力,神经生长因子(NGF)及其前体蛋白表达水平,探索其作用机制。结果 行为学测试结果显示加味开心散可明显缩短小鼠Morris水迷宫定位导航潜伏期,增加空间探索中穿越平台次数,减少上台前游泳距离;降低主动回避实验中明暗箱穿梭错误次数。降低ChE活性,提高NGF的表达水平。水醇共提物效果优于水提物。结论 加味开心散可明显增强多因素神经损伤痴呆小鼠的学习记忆能力,其作用的机制可能与抑制乙酰胆碱降解,提升神经因子表达有关。Abstract: OBJECTIVE To evaluate the effect of Jiawei Kaixin San(JWKXS) on learning and memory abilities of multiple neuronal damage induced dementia mice and explore its mechanism. METHODS Dementia mice model was established via multiple neuronal damages, then the model mice were treated with water extracts, and water and ethanol combined extracts of JWKXS for 10d, while huperzine (0.05mg/kg) was applied as positive drug. The abilities of learning and memory were evaluated by behavioral tests, such as Morris water maze test and active avoidance test. In addition, cholinesterase(ChE) activities, superoxide dismutase(SOD) and protein expression levels of nerve growth factor(NGF) with its precursor in cerebral cortex of model mice were detected. RESULTS Behavioral tests showed JWKXS obviously shortened the incubation time of navigation and positioning, increased the times across platform and decreased swimming distances in Morris water maze test. In active avoidance test, the shuttle error numbers of model mice decreased with the treatment of JWKXS. In cerebral cortex, ChE activities were down-regulated while NGF levels were up-regulated. The effects of water and ethanol combined extract were better than the water extracts. CONCLUSION JWKXS can significantly improve the learning and memory ability of dementia mice induced by multiple neuronal damage. Its mechanism might be related to the inhibition of acetylcholine degradation and up-regulation of nerve factor expression.