| ObjectiveTo investigate the effect of electroacupuncture?EA?combined with medication?Donepezil?on learning-memory ability and gene expression of?-amyloid?A??clearance-related factors in the hippocampus in senescence-accelerated mouse prone 8?SAMP8?mice,so as to explore their synthetic effect in improving dementia of Alzheimer's disease?AD?.MethodsThe male SAMP8 mice?30-week-old?were randomly divided into model,medication,EA group and combined group?n=7 mice in each group?,and other 7 senescence-resistant 1?SAMR1?mice were used as the control group.EA?2 Hz,1 mA,continuous wave?was applied to“Baihui”?DU 20?and“Yintang”?EX-HN3?for 15 min,once daily,6 days a week for 4 weeks.Mice of the EA+medication group received gavage of Donepezil(1.3 mg·kg-1·d-1),once daily,6 days a week for 4 weeks.The Morris water maze?MWM?task?including place navigation tests and space exploration trials?was used to assess the mouse's learning-memory ability.Transmission electron microscope was uesed to observe hippocampus tight junction?TJ?and basement membrane.Histopathological changes of hippocampus tissue were observed by HE staining.The activities of acetylcholinesterase?AChE?in hippocampus were detected with immunohistochemistry.The expression levels of MMP-9,LRP-1,Pgp,A?,ZO-1,Claudin-5 and Occludin mRNAs of the hippocampus tissue were detected by quantitative real-time PCR.ResultsTJ and basement membrane in the control group,acupuncture group and combined group were better than those in the model group and the drug group.HE staining showed scatted and loose arrangement of neurons in the hippocampus,with reduction of number of cell layers and unclear nucleoli,which was relatively milder in the control,EA,medication and combined groups.AChE was the most in the combined group,and then the drug group and the control group,the acupuncture group?P<0.01?.Compared with the control group,the average escape latency of place navigation tests,and the expression levels of MMP9 and A?mRNAs were significantly increased?P<0.01?,and the number of platform quadrant-crossing times of space exploration trials,and the expression levels of LRP-1,Pgp and ZO-1,Claudin-5,Occludin mRNAs considerably decreased in the model group?P<0.01?.After the intervention,the learning-memory ability was significantly improved?P<0.01?.The expression levels of MMP-9,A?mRNAs were obviously down-regulated?P<0.01?in the EA,and combined group,and those of LRP-1,Pgp,ZO-1,Claudin-5 and Occludin mRNAs were remarkably up-regulated?P<0.01?.The expression level of A?mRNA was obviously down-regulated?P<0.01?in the medication group,and those of LRP-1,Pgp mRNAs were remarkably up-regulated?P<0.01?.Compared with the EA group,the learning-memory ability was significantly improved?P<0.05,P<0.01?and the expression level of A?mRNA was decreased in the combined group?P<0.05?.Compared with the medication group,the expression of MMP-9 mRNA was obviously decreased?P<0.01?and those of LRP-1,Pgp,ZO-1,Claudin-5 and Occludin mRNAs were remarkably increased?P<0.01?in the EA group.The therapeutic effects of combine were apparently superior to that of simple medication in shortening the escape latency and in down-regulating the expression of MMP9 and A?mRNAs?P<0.05,P<0.01?,and in increasing the number of platform quadrant-crossing times?P<0.01?,and expression levels of LRP-1,Pgp,ZO-1,Claudin-5 and Occludin mRNAs?P<0.01?.ConclusionEA combined with Donepezil can enhance the effect of improving learning-memory ability in SAMP8 mice possibly relate to regulating expression of MMP-9,LRP-1,Pgp,ZO-1,Claudin-5 and Occludin mRNAs by EA and strengthening the effect of Donepezil in transporting A?via blood-brain barrier. |
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