Objective To investigate the effect of electroacupuncture(EA) combined with Donepezil on learning-memory ability and gene expression of β-amyloid(Aβ) 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).Methods Male SAMP8 mice(30-week-old) were randomly divided into model

medication and EA+medication groups(n=6 mice in each group)

and other 6 senescence-resistant 1(SAMR1) mice were used as the control group. Mice of the medication and EA+medication group received gavage of Donepezil(1.3 mg·kg

(-1)

·d(-1)·d

(-1)

) once daily for 4 weeks. EA(2 Hz

1 mA) was applied to "Baihui"(GV20) and "Yintang"(EX-HN3) for 15 min

once daily

6 days a week for 4 weeks for rats in the EA+medication group. The Morris water maze(MWM) task(including place navigation tests and space exploration trials) was used to assess the mouse's learning-memory ability. Histopathological changes of hippocampus tissue were observed by H.E. staining. The expression levels of matrix metalloprotein 9(MMP-9)

low density lipoprotein receptor-related protein-1(LRP-1)

P-glycoprotein(Pgp

an important drug transporter responsible for multidrug resistance)

Claudin-5(a component of tight junction strands that serves as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets of blood-brain barrier

BBB) and Aβ mRNAs of the hippocampus tissue were detected by quantitative real-time PCR.Results Compared with the control group

the average escape latency of place navigation tests

and the expression levels of MMP-9 and Aβ 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 Claudin-5 mRNAs considerably decreased in the model group(P

<

0.01). After the intervention

the learning-memory ability was significantly improved in the medication and EA+medication groups(P

<

0.01

P

<

0.05)

the expression levels of Aβ mRNAs in the medication and EA+medication groups and MMP-9 mRNA in the EA+medication group were obviously down-regulated(P

<

0.01)

and those of LRP-1 and Pgp mRNAs in the medication and EA+medication groups and Claudin-5 mRNA in the EA+medication group were remarkably up-regulated(P

<

0.05

P

<

0.01). The therapeutic effect of EA+medication was apparently superior to that of simple medication in shortening the escape latency(P

<

0.05

P

<

0.01) and in down-regulating the expression of MMP-9 and Aβ mRNAs(P

<

0.01)

and in increasing the number of platform quadrant-crossing times(P

<

0.01)

and expression levels of LRP-1

Pgp and Claudin-5 mRNAs(P

<

0.01). H.E. 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 medication and EA+medication groups. Conclusion EA can enhance the effect of Donepezil in improving learning-memory ability in AD mice possibly by regulating expression of MMP-9

LRP-1

Pgp and Claudin-5 mRNAs and strengthening the effect of Donepezil in transporting Aβ via BBB.