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Objective:The present study was designed to investigate the neuroprotective effect of mesenchymal stem cells(MSC)which incubated with tanshinone IIA onβ-amyloid(Aβ)-induced leing and memory impairment in rats,and further explore the underlying potential mechanisms. Methods:60 healthy male SD rats were randomly divided into 4 groups:sham-operated group,model group,MSC group,MSC+tanshinone group IIA(n=15).The rats of model group were injected into the hippocampal with aggregation of 5 μL Aβ25-35(2 μg·μL-1)to establish the model of leing and memory impairment. 1 week after surgery,the MSC were injected into the hippocampus,while the rats of model group were injected with volume-matched DMEM,instead. 2 weeks after surgery, Morris water maze(MWM)test was applied to evaluate spatial leing and memory ability of rats, then the rats were sacrificed. The survival status of hippocampal neurons was detected by HE and Tunel staining;the formation of hippocampal senile plaques was detected by thioflavin S staining;the protein expression of Aβ1-42,p-Tau and AMPK in mouse hippocampus were detected by West blot, respectively;the expression of AMPK mRNA was detected by PCR and the activity of SOD,T-AOC, GSH-PX and content of MDA in plasma by the kits.Results:Compared with sham-operated group, the mean escape latency was markedly increased and the time percentage in target quadrant showed notable decrease in model group;large number of the formation of senile plaque in the hippocampus was detected;the number of surviving neurons in hippocampus was significantly decreased and the apoptosis increased;the protein expression of Aβ1-42 and p-Tau were increased;the mRNA expression and protein levels of AMPK was decreased;the activity of SOD,T-AOC,GSH-PX were decreased and content of MDA increased in plasma.However,compared with model group,the escape latency of MSC group and MSC+Tanshinone group rats was shorter,time percentage in the target quadrant and target quadrant frequency were markedly increased;moreover,the formation of senile plaque in the hippocampus was decreased;the number of surviving neurons in hippocampus was significantly increased;the protein expression of Aβ1-42 and p-Tau were decreased;the mRNA expression and protein levels of AMPK was increased;the activity of SOD,T-AOC,GSH-PX were increased and content of MDA decreased in plasma.And MSC+tanshinone group was more significant than the MSC group. Conclusion:Under the experimental conditions,MSC incubated with tanshinone ⅡA significantly ameliorates spatial leing and memory impairment and reduce Aβaggregation and tau protein phosphorylation levels induced by Aβ25-35 in rats,and its potential mechanism may be related toanti-oxidative stress.