Abstract: 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 41th 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.

Key words: tetramethylpyrazine, D-galactose, Alzheimer's disease, AD model, cholinergic system