| Objective:To observe the effect of GEPT extract on behavior impairments, and expression of hippocampus of Choline acetyltransferase and acetyclholine esterase in APP/PS1transgenic mice.Method:The mice used in this study are purchased at the Institute of Zoology Chinese Academy of Sciences. AD model mice were3-mo nth-old APPswe/PS1dE9double transgenic mice, Normal group were the same month old C57BL/6non-transgenie wild-type mice.The mice were bred in traditional Chinese medicine pharmacology laboratory environment barrier house of Beijing university of Chinese medicine DongZhiMen hospital. The double transgenic mice were randomly assigned5groups:model group (n=10), donepezil HCL group (n=10), GEPT low-dose group (n=10), GEPTdosage group (n=10) and the GEPT high-dose group (n=10).The same month old C57BL/6mice as a positive control group (n=10). Normal group and model group were given equal volume of0.5%sodium carboxymethyl cellulose (CMC) gavage, positive control group were given donepezil0.92mg·kg-1·d-1gavage, low-dose group were given GEPT1.22g·kg-1·d-1gavage, mid-dose group were given GEPT2.44g·kg-1·d-1gavage, high-dose group were given GEPT4.88g·kg-1·d-gavage. The mice were given medicines from the age of3months lasting6months, and from Monday to Saturday every week, once a day. When feeding to9months, observed the behavior change of the mice by morris water maze and step down test. After the behavioral experiments, used the westen blot and image analysis method to determine the content of ChAT and Ach inside hippocampus of mice. Experimental data were analysed by SPSS20.0statistics software. Measurement data using mean±standard deviation (x±s), according to analysis of data,if the sample data conforms to normal distribution and homogeneity of variance, use single fac tor analysis of variance (one-way ANOVA), if do not accord with normal distribution, then use Kruskal WallisH inspection;analyse count data by chi-square. When P<0.05said have significant difference,when p<0.01said have a extremely significant difference.Results:The results o f step down test show that in the training process of the first day, the number of errors of the model mice, compared with the normal group was significantly different (p=0.038). In the test of the second day, the number of error is less than the first day in each group, but the errors of model group mice are more than the normal group and other drug groups, low-dose group and mid-dose group’s results close to the normal group, there was no significant difference between groups (P=0.133).Morris water maze results: Inorientation navigation experiments of5days, incubation period of mice in the first day of each group was not different (P=0.063), swimming strategy with random type and marginal strategy is given priority, but with the increase of training frequency, average latency time in general is on the decline, tendency type and straight strategy of each group has increased. Fromthe second day to the fifthday, the latent time of the model group,compared with the normal group has significant difference or extremely significant difference,(d2P=0.009, d3P=0.002, d4P=0.000, d5P=0.000). Donepezil group compared with the model group have significantly difference or extremely significant difference(d3P=0.012, d4P=0.002) in the third day and the forth day; there was a significant difference (d4P=0.011, d5P=0.048) in small dose group,compared with the model group, in the forth day and the fifth day of experiments; middle dose group compared with the model group was extremely significantly different (d4P=0.003, d4P=0.001) in the forth day and the fifth day; the high-dose group compared with the model group was extremely significant different (d3P=0.003)in the third day; In Space exploration experiment,the number of across the platform and standing time of target quadrant of the transgenic mice were less than the normal group. The number of across the platform and standing time oftarget quadrant of the model group compared with the normal group were extremely significantly different, P values were0.004and0.000respectively,the result of the target quadrant standing time the mid-dose group compared with the model group was shown the extremely significant difference (P=0.003); In the sixthday, there was a significant differences (P=0.004) in swimming strategy of trend type in normal group compared with the model group, each dose group compared with the model group there was no significant difference (Donepezil group P=0.091, low-dose group P=0.656, mid-dose group P=0.546, high-dose group P=0.165). The ChAT and AchE content determination experiment:ChAT in hippocampusof model group than in the normal group was significantly different (P=0.037), in Donepezil group, GEPT mid-dose group and high-dose group,ChAT content increase, but there was no significant difference compared with the model group (Donepezil group P=0.110, low-dose group P=0.996, mid-dose group P=0.156, high-dose group P=0.283). AChE content is relatively high in model group and low in GEPT low-dose group and mid-dose group compared with the positive control group, but each group was not significantly different (Normal group P=0.881, Donepezil group P=0.337, low-dose group P=0.305, mid-dose group P=0.165, high-dose group P=0.881).Conclusion:1. AD model mice suffered from cognitive memory impairment in nine months, and accompanied by the ChAT activity weakened in hippocampus,suggcsting that cholinergic damage is related to the ability of learning and memory disorders.;2. The GEPT can effectively improve the cognitive dysfunction caused by cholinergic damage of APP/PS1transgenic mice.The mechanism may that GEPT can increase ChAT activity, thereby increasing the amount of Ach to improve the cholinergic systemdamage, eventually improve the AD model mice’s learning and memory ability. The mid-dose group’s effect was relatively better, the large dose group and the small dose group’s were poorer. |
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