宽叶缬草中volvalerenal K对APP双转基因痴呆小鼠学习记忆的改善

Improving effect of volvalerenal K from Valeriana officinalis Linn.var. latiofolia miq on learning and memory abilities in APPswe/PS1E9 double-transgenic AD mouse model

目的:研究宽叶缬草中volvalerenal K对APPswe/PS1E9双转基因阿尔茨海默病小鼠模型学习记忆能力的改善及对胆碱能神经系统胆碱酶变化的影响。方法:将SPF级75只3月龄APPswe/PS1E9双转基因雄性小鼠随机分成5组,分别为模型组(0.5%CMC)、多奈哌齐组(1.30 mg·kg^(-1)·d^(-1))、volvalerenal K低、中、高剂量组(0.65,1.30,2.60 mg·kg^(-1)·d^(-1)),15只C57BL/6J雄性小鼠作为正常对照组,每天灌胃(ig)1次,连续给药90 d。采用Morris水迷宫测定小鼠空间学习记忆能力,通过比色法测定小鼠脑组织中乙酰胆碱(Ach)、乙酰胆碱酯酶(AchE)及胆碱乙酰化酶(ChAT)的含量。结果:在水迷宫实验中,模型组小鼠的学习记忆能力均有所下降,胆碱酶Ach,ChAT的含量均明显下降(P<0.01),而AchE含量升高(P<0.01);阳性药对照组、给药中剂量、高剂量组小鼠学习记忆能力明显提高(P<0.01),且Ach,ChAT含量均有所提高(P<0.01),而AchE含量则出现下降(P<0.01)。结论:天然产物volvalerenal K能改善阿尔茨海默病模型小鼠的学习记忆能力,作用机制可能与调控胆碱能神经系统相关酶有关。

Objective： To study the improving effect of volvalerenal K from Valeriana officinalis Linn. var.latiofolia miq on learning and memory abilities and the changes of related enzymes of cholinergic system in APPswe /PS1E9 double-transgenic AD mouse model. Methods： Seventy-five Class SPF APPswe / PS1E9 double transgenic dementia male mice at age of 3 months were randomly divided into 5 groups（ 15 mice / group）,namely,model group（ 0. 5% CMC）,donepezil group（ 1. 30 mg·kg（-1）·d（-1））,volvalerenal K low dose（ 0. 65 mg·kg- 1·d- 1）,middle dose（ 1. 30 mg·kg- 1·d- 1） and high dose group（ 2. 60 mg·kg（-1）·d（-1））. Fifteen C57BL/6J male mice were used as the normal control group. Intragastric administration was performed for consecutive 90 d at a frequency of once per day. Learning and memory abilities were evaluated by Morris water maze. The acetylcholine（ Ach）,acetylcholine transferase（ ChAT）,and acetylcholinesterase（ AchE） in the brain tissues were also determined by colorimetry. Results： The learning and memory abilities of the mice and the contents of Ach and ChAT decreased in the model group（ P〈0. 01）,while AchE increased（ P〈0. 01）. Compared with the model group,Ach and ChAT in the positive control group,high dose group and medium dose group increased（ P〈0. 01）,while AchE decreased（ P〈0. 01）. Conclusion： The natural product,volvalerenal K,can improve the learning and memoryabilities of APPswe / PSΔE9 double-transgenic mice,and the mechanism may be related to the regulation of related enzymes in cholinergic system.