参乌胶囊对东莨菪碱模型大鼠学习记忆能力和脑内胆碱能系统的影响

Effects of Shenwu Capsule on Learning-Memory Ability and Cholinergic System in Model Rats Induced by Scopolamine

目的观察中药新复方参乌胶囊对东莨菪碱致记忆障碍模型大鼠学习记忆及脑内胆碱能系统的影响。方法将Wistar大鼠随机分为对照组、东莨菪碱模型组、多奈哌齐组(阳性对照药)、参乌胶囊小剂量(0.2g.kg-1)、中剂量组(0.6g.kg-1)、大剂量(1.8g.kg-1)6组,灌胃给药2周后,除正常对照组腹腔注射生理盐水外,其他各组注射东莨菪碱2mg.kg-1,20min后进行Morris水迷宫和跳台测试,测试结束后处死,取其脑皮层、海马,应用生化方法测定乙酰胆碱酯酶(AChE)活性,放射免疫法测定胆碱乙酰基转移酶(ChAT)活性,放射配基法测定M受体结合力。结果参乌胶囊灌胃给药能够提高东莨菪碱模型大鼠学习记忆能力,缩短Morris水迷宫游泳时间及距离,延长跳台实验的潜伏期,减少错误次数(P<0.05);并能降低模型大鼠脑皮层AChE活性,提高海马ChAT活性,增强皮层和海马M受体结合力(P<0.05,P<0.01)。结论参乌胶囊可以改善东莨菪碱模型大鼠的记忆障碍,其机制可能与提高M受体结合力、增强ChAT活性、抑制AChE活性有关。

OBJECTIVE To investigate the effects of Shenwu capsule （SW）,a new Chinese herb combination drug,on learning-memory ability and cholinergic system in model rats induced by scopolamine （Scop）.METHODS Wistar rats were randomly divided into normal control group,Scop model group,Donepezil group （positive control drug）,low,medium and high doses of SW groups （0.2,0.6 and 1.8 g·kg^-1）.The drugs were intragastrically administered to rats for two weeks.On day 14,after intraperitoneal injection of scopolamine,rats were subjected to Morris water maze and step-down tests.The activity of acetylcholinesterase （AChE） in cerebral cortex was measured by a biochemical method,choline acetyl transferase （ChAT） and M-cholinergic receptors were determined by radioimmunoassay and radio-ligand method,respectively.RESULTS Compared with model group,a significant decrease of swimming time and distance in Morris water maze test was observed in SW groups.SW also increased the latencies and decreased the number of errors in step-down task （P〈0.05）.SW decreased AChE activity in cerebral cortex,and increased ChAT activity and M-cholinergic receptor binding in the hippocampus and cerebral cortex of model rats （P〈0.05,P〈0.01）.CONCLUSION SW effectively improved learning-memory ability in model rats induced by scopolamine.The mechanism might be related with the enhancement of M-receptors and ChAT and the inhibition of AChE in the brain.