川芎嗪对AD模型小鼠海马胆碱能系统的影响

Effects of Tetramethylpyrazine on the Hippocampal Cholinergic System in D-galactose Induced Mice Model with Alzheimer's Disease

目的探讨川芎嗪对D-半乳糖(D-gal)所致AD模型小鼠海马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造模。第3周起各组分别灌胃生理盐水(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)。给药结束后进行水迷宫训练,24h后进行学习记忆功能测试和海马胆碱乙酰基转移酶(chAT)与乙酰胆碱酯酶(AchE)活性测定以及M受体放射性配基结合分析。结果与正常对照组相比,D-gal模型组小鼠学习记忆能力和M受体含量均明显下降(P<0.05～0.01)。模型组chAT和AchE活性也有轻微下降,但与对照组比较差异无统计学意义。给予川芎嗪可明显改善AD模型小鼠的学习记忆功能,增强海马chAT活性(P<0.01)和AchE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,改善海马胆碱能系统功能。

Objective To investigate the effects of tetramethylpyrazine on the hippocampal cholinergic system in D-galactose induced Alzheimer＇ s disease in mice model. Methods C57BL/6J mice were given subcutaneous injection of 2% D-galactose for 40 days （100 mg·Kg^-1·d^-1）. Normal saline, tetramethylpyrazine and Huperzine A respectively were given by intragastric administration in different study groups from the third week. The mice were trained to find the platform in the water maze on the 41 th day. After 24 hours, learning and memory ability was tested. Choline acetyltransferase （chAT） activity , acetylcholinesterase （AchE） activity , the binding sites（Bmax） and the affinity（KD） of M-cholinergic receptor in the hippocampi were determined. Results The learning and memory dysfunction and reduced M-cholinergic receptor binding sites were found in the model group as compared with the normal control group （P〈 0.05 -0.01 ）. Although chAT activity and AchE activity were mildly lowered in the model group, there was no statistical significance when compared with the control group. The tetramethylpyrazine could markedly attenuate cognitive dysfunction, elevate chAT activity （ P 〈 0.01 ）, AchE activity （ P 〈 0.05 ） and M-cholinergic receptor binding sites （ P 〈 0. 005 ） in the hippocampi of mice treated with D-galactose. Conclusion The tetramethylpyrazine can significantly improve the hippocampal cholinergic system function, and thus enhance the learning and memory ability in D-galactose induced Alzheimer＇ s disease model mice model.