人参、银杏叶提取物对PDAPP^(V717I)转基因小鼠海马乙酰胆碱和单胺类神经递质水平的影响

Effects of Extracts of Ginseng and Ginkgo Biloba on Hippocampal Acetylcholine and Monoamines in PDAPP^(V717I) Transgenic Mice

目的探讨人参、银杏叶提取物配伍(脑维康,NWK)对APP转基因小鼠海马神经递质水平的影响及其可能机理。方法以PDAPPV717I转基因小鼠为老年性痴呆动物模型,给药组小鼠每天1次灌胃给予NWK(31mg/kg和62mg/kg)12周。以高效液相电化学方法检测小鼠海马乙酰胆碱(ACh)含量及海马单胺类神经递质及其代谢产物的含量。结果与非转基因小鼠比较,转基因组小鼠海马ACh、5-羟吲哚乙酸(5-HIAA)水平均显著降低(P<0.01),5-羟色胺(5-HT)水平显著升高(P<0.05),去甲肾上腺素、多巴胺水平分别升高14.6%和17.7%。给药后NWK两个剂量组小鼠海马ACh含量均较转基因非给药组显著升高(P<0.05);NWK高剂量组小鼠海马5-HT水平显著下降(P<0.05)。结论NWK对APP转基因小鼠海马ACh和单胺能系统、特别是胆碱能和5-HT能系统具有明显的调节作用,这可能是其改善多种AD模型动物学习记忆能力的机理之一,从而对老年性痴呆有一定的治疗作用。

Objective To study the effects and its possible mechanism of Naoweikang （NWK）, a composite of ginseng and ginkgo extracts, on hippocampal neurotransmitters in APP transgenic mice. Methods P- DAPPv717I transgenic mice were taken as the model of Alzheimer＇s disease （AD） and be treated with different doses of NWK （31 mg/kg and 62 mg/kg） respectively by gastrogavage once per day for 12 weeks. Contents of hippocampal acetylcholine （ACh）, monoamine neurotransmitters and their metabolites were determined with high performance liquid chromatography. Results Compared with nontransgenic mice, the levels of ACh and 5- HIAA in hippocampus of transgenic mice lowered significantly （P 〈 0.01 ）, while 5-HT increased significantly （ P 〈 0.05）, and the levels of norepinephrine and dopamine increased by 14.6 % and 17.7 %, respectively. After 12-week administration, the ACh level increased significantly in the two NWK treated groups （P 〈 0.05）, and the 5-HT level in the high dose NWK treated group decreased （P 〈 0.05）, as compared with those in the untreated transgenic mice. Conclusion NWK shows a significant regulatory effect on the activities of hippocampal acetylcholine and monoamine system, especially the cholinergic and 5-HT systems, in APP transgenic mice, which might be one of its mechanisms in improving learning and memory of AD model, and therefore, NWK might exert certain curative effect on AD.