Effects Of Donepezil On Learning And Memory In OSAS Rats And Its Mechanism

Objective: By simulating chronic intermittent hypoxia(CIH)environment to establish OSAS rat model.Observe the expression of SYP and PSD-95 protein in hippocampus of OSAS rats treated with Donepezil and explore the therapeutic effect and mechanism of donepezil on OSAS rats.Methods: 32 adult rats were randomly divided into the normal group,the OSAS model group,the saline control group and the donepezil intervention group,with 8 rats in each group.The OSAS model rats were established by using the hypoxic--module to simulate the CIH environment.After the model rats were successfully established,the behavioral changes of rats were detected by the Morris water maze(MWM).Immunohistochemical method was used to detect the expression sites of SYP and PSD-95 protein in the hippocampus of rats.Meanwhile,Western Blot(WB)was used to detect the expression level of SYP and PSD-95 protein in the hippocampus of rats.Results: After the modeling,the OSAS rats with hypoxic environment appeared symptoms including rise of breathing,faster breathing,reduced activity,sleepiness and performance.In the hypoxic environment,the rat rail artery blood oxygen saturation for the average was(71.63±3.31)%.Compared with the reoxygenation environment(95.38±1.80)%,the oxygen saturation of the rat rail artery decreased significantly,and the decrease was more than 4%,reaching the standard of OSAS animal model.The water maze experiment in the navigation experiment indicated that from the first day of the experiment,the escape latency of the rats in the model group compared with the normal group,the intervention group were significantly prolonged(from the first day to the fifth day,the F-measure were 9.74,4.81,15.91,5.85,32.29 respectively,P<0.05);The escape latency of the intervention group was significantly less than the model group(P<0.05).There was no significant difference between the model group and saline control group(P>0.05).The escape latency in the space exploration experiment showed that compared with the normal group(3.53±0.82)and intervention group(3.34±0.78),the frequency of crossing the original platform of the model group(1.91±0.90)were significantly reduced(,P<0.05);While,the model group and the control group had no significant difference in the number of cross platform(P>0.05).In immunohistochemical experiment,the positive expression of PSD-95 was observed in neurons of hippocampal CA1 area of OSAS rats,which was brown and granular like substance,mainly located in cytomembrane of neurons.The brown yellow granules were dyed deep and densely in the normal group and the intervention group,and the color was shallow in the model group and the control group,and the distribution was thinner.SYP was mainly located in the neurites mat area of OSAS rat hippocampus.The positive expression was brown and punctate granules,and distributed densely.In the normal group and the neurites mat area of the intervention group,the yellow punctate granules were deep stained,while in the model group and the control group,the brown granules were pale.In Western blotting experiments,gray value of expression in the rat hippocampus region of PSD-95 protein of the model group and the normal group were(0.32 + 0.058)and(0.58 + 0.046)respectively.The results of model group decreased and there was statistically significant(P<0.05);Compared with the model group,gray rat hippocampus PSD-95 protein expression value of the intervention group(0.53 + 0.08)significantly increased,there was statistical significance(P<0.05))between the model and intervention group;Between the model group and the control group,the expression of the gray value of PSD-95 protein showed no significant difference(P>0.05).There were no significant difference between four groups of the expression of SYP protein in hippocampus of rats in the gray value(F=0.29,P>0.05);The difference between the normal group(4.03 + 3.82)and model group(2.89 + 2.32),model group and intervention group(2.71 + 2.59),the gray value of SYP protein expression were no statistical significance(P>0.05).Conclusion: Donepezil can improve the learning and memory ability of OSAS rats.It,s mechanism may be related to the increase of the content of PSD-95 protein in the hippocampus region,thereby improving synaptic plasticity.