川芎嗪对D-半乳糖损伤模型小鼠学习记忆及胆碱能系统的影响

Effect of Tetramethylpyrazine on Learning,Memory and Cholinergic System in D-galactose-lesioned Mice

目的探讨川芎嗪对D-半乳糖(D-galactose,D-gal)损伤模型学习记忆和胆碱能系统功能的影响。方法C57BL/6J小鼠颈背部皮下注射2%D-gal100mg·kg-1·d-1,连续40d制造D-gal损伤模型。第3周起各组分别用生理盐水(正常对照组、模型组)、川芎嗪(高、低剂量组)和哈伯因(阳性对照组)灌胃。第6周起进行Morris水迷宫测试,连续5d。行为测试结束后,进行大脑皮层乙酰胆碱酯酶(acetylcholinesterase,AchE)活性测定和M受体的放射性配基结合分析。结果与正常对照组相比,D-gal模型组学习记忆能力、AchE活性和M受体含量均明显下降(P<0.05),川芎嗪尤其是在100mg·kg-1·d-1剂量时可明显改善学习记忆功能,增强胆碱酯酶活性(P<0.05),上调M受体数目(P<0.005)。结论川芎嗪可明显提高模型小鼠的学习记忆能力,改善中枢胆碱能系统功能。

To explore the effect of tetramethylpyrazine on learning,memory,and cholinergic system in D-galactose-lesioned mice.Methods C57BL/6J mice were given subcutaneous injection of2%D-galactose for40days(100mg ·kg -1 ·d -1 ).Normal saline,tetramethylpyrazine(TMP)and Huperzine A(HupA)were given respectively by intragastric administration in different study groups from the third week on.Learning and memory ability were tested by Morris water maze for5days at the sixth week.Acetylcholinesterase(AchE)activity,the binding sites(Bmax)and the affinity(KD)of M-cholinergic receptor were determined.Results The learning and memory dysfunction,with lowered AchE activity and M-cholinergic receptor binding sites were found in the model group as compared with the normal control group.The tetramethylpyrazine,especially at the dose of100mg ·kg -1 ·d -1 ,could markedly attenuate cognitive dysfunction,while elevate the lowered AchE activity(P<0.05)and M-cholinergic receptor binding sites(P<0.005)in the cerebral cortex of mice treated with D-galactose.Conclusions The tetramethylpyrazine can significantly improve central cholinergic system function,and thus enhance the learning and memory ability in D-galactose-lesioned mice.