| Objective:Zhuang-yuanwan water extract were applied to APPswe/PS1De9double-transgenic mice of Alzheeimer's disease,the memory ability and spatial ability of the Zhuang-yuanwan water extract were analyzed by Mirror water maze test in mice with double-transgenic AD mice model.The expression of A?42,ACh,AChE,ChAT and Bcl-2/Bax in hippocampus of brain tissue can evaluate the pharmacological effects and mechanism of Zhuang-yuanwan water extract on double-transgenic AD mice model.Methods:3 months old APPswe/PS1De9 double-transgenic mice 50,male and female half,were randomly divided into 5 groups:model group?MG?,aricept group?AG?,Kai-xinsan group?KG?,Zhuang-yuanwan low-dose group?ZLG?and high-dose group?ZHG?.And the same age with the same background male and female halfC57BL/6J mice 10,normal control group?NCG?.The AG,KG,ZLG according to human and mice dose fold conversion.The dose was 2mg·kg-1·d-1,2g·kg-1·d-1,1.5 g·kg-1·d-1.ZHG according to human and mice 4 times the dose conversion.The dose was 6 g·kg-1·d-1.The administration volume is 0.02mL·g-1·d-1.The NCG and MG were given the same volume of saline every day.After 6 months of continuous administration,Mirrors water maze was used to analyze the memory and spatial ability of mice.At the end of the experiment,the brain was perfused and the hippocampus of the brain was separated and the tissue protein was extracted.The expression of A?422 was detected by ELISA.The expression of ACh,AChE and ChAT was measured by microplate method and colorimetry method to evaluate the function of cholinergic system.The ratio of Bcl-2/Bax was determined by Western blot.Results:?1?Mirros Water Maze Experiment:Compared with NCG,the latency and swimming distance of the MG were significantly prolonged?P<0.01 or P<0.05?,the duration of the quadrant of the original platform was shortened?P<0.01?.Compared with MG,the latency and swimming distance of the AG,KG,ZLG,ZHG were significantly shortened?P<0.01 or P<0.05?,the duration of the quadrant of the original platform was Prolonged?P<0.01?.?2?Expression of related indexes in hippocampus of brain tissue:Compared with NCG,the expression of A?422 in MG increased?P<0.01?,Compared with MG,the expression of A?422 in AG,KG,ZLG,ZHG decreased?P<0.01 or P<0.05?.Compared with NCG,the expression of ACh,AChE,ChAT in MG decreased?P<0.01?,Compared with MG,the expression of ACh,AChE,ChAT in AG,KG,ZLG,ZHG increased?P<0.01 or P<0.05?.AG can decreased the expression of AChE?P<0.05?.KG,ZLG,ZHG can increased the expression of ChAT?P<0.01 or P<0.05?.Compared with NCG,the ratio of Bcl-2/Bax in MG decreased?P<0.01?.Compared with MG,the ratio of Bcl-2/Bax in AG,KG,ZLG,ZHG increased?P<0.01 or P<0.05?.Conclusion:Zhuang-yuanwan water extract can improve the memory and spatial ability of APPswe/PSI1dE9 double-transgenic AD model mice;reduce the expression of A?422 in hippocampus of brain tissue;By increasing the activity of ChAT to increase the expression of ACh,thereby improving the function of cholinergic system;improve the ratio of Bcl-2/Bax in hippocampus of brain tissue. |
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