人参、银杏叶提取物对β-淀粉样蛋白_(1-40)毒性损伤大鼠全脑神经递质的影响

目的探讨给予人参、银杏叶提取物(脑维康)前后,β-淀粉样蛋白(β-amyloid peptide,Aβ)1-40毒性损伤大鼠全脑乙酰胆碱、单胺类递质及其代谢产物水平的变化和可能机制。方法以双侧海马CA1区注射Aβ1-40(每侧4 g.L-1)大鼠为模型,给药组大鼠每天灌胃给予脑维康(15.5、31、62mg.kg-1)4 wk。以改进的柱前、柱后双酶柱结合高效液相电化学方法检测大鼠全脑乙酰胆碱含量,以高效液相电化学方法检测大鼠全脑单胺类神经递质及其代谢产物的含量。结果双侧海马注射Aβ1-404 wk后,大鼠全脑乙酰胆碱、5-羟色胺含量明显降低(P<0.05~0.01),多巴胺、去甲肾上腺素表现下降趋势。给药4 wk后,脑维康各给药组大鼠全脑乙酰胆碱含量较模型组大鼠升高(P<0.05~0.01),多巴胺、5-羟色胺水平无变化,高香草酸、5-羟吲哚乙酸水平呈下降趋势,其中脑维康15.5 mg.kg-1组高香草酸含量下降(P<0.05)。结论脑维康可升高Aβ1-40毒性损伤大鼠脑内的乙酰胆碱水平,对单胺类递质代谢有一定的调节作用。该药改善大鼠学习记忆损伤的机制可能与其保护脑内胆碱能和单胺能系统或干预神经递质的合成、摄取和降解等作用有关。

Effect of combination of extracts of ginseng and ginkgo biloba on neurotransmitters in whole brain of β-amyloid peptide1-40treated rat

Aim To detect the effect of a combination of extracts of ginseng and ginkgo biloba(Naoweikang,NWK) on acetylcholine,monoamines and their metabolites in β-amyloid peptide(Aβ)_(1-40) treated rats and the potential mechanisms.Methods A 1-month NWK(15.5,31 and 62 mg·kg~(-1),respectively) administration to rats was performed daily after bilateral injection of Aβ_(1-40)(4 g·L~(-1) for each side) into hippocampus.Acetylcholine(ACh) was determined with an improved HPLC-ECD method,which is combined with two immobilized enzyme reactors.Monoamines and their metabolites were also determined with HPLC-ECD.Result Compared with shams,ACh and serotonin(5-HT) in whole brains in models decreased significantly(P<0.05～0.01) after bilateral injection of Aβ_(1-40) and there were decreasing tendencies in dopamine(DA) and norepinephrine(NE).After NWK administration(15.5,31 and 62 mg·kg~(-1),respectively),ACh increased significantly in rats in each NWK administrated-group compared with models(P<0.05～0.01).Although DA and 5-HT didn′t significantly change in rats in each group,there were decreasing tendencies in homovanillic acid(HVA) and 5-hydroxyindole acetic acid(5-HIAA).Meanwhile,HVA in rats in 15.5 mg·kg~(-1) administrated group significantly decreased(P<0.05).Conclusion NWK significantly increased the level of ACh in Aβ_(1-40) treated rats and modulate the metabolism of monoamines meanwhile.The mechanisms of NWK improving behavioral impairment of Aβ_(1-40) treated rats might be due to its protecting the neurotransmitter systems or interfering the synthesis,uptaking and degradation of neurotransmitters in rat brain.