Protective effect of tanshinoneIIA on dopaminergic neurons in mouse model of Parkinson's disease and its mechanism

Objective To explore the effects of tanshinoneⅡ A on the injury of dopaminergic neurons of Parkinson's disease(PD)mouse model induced by 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP),and to clarify the possible mechanism of its protective effects on dopaminergic neurons.Methods 60C57BL/6N mice were randomly divided into control group,PD model group and tanshinoneⅡ A group(n=20).The mice in PD model group and tanshinoneⅡ A group were treated with MPTP to establish PD models.The bebavior of the mice in various groups was observed.The number of tyrosine hydroxylase(TH),cd11 b,p47-phox,and inducibleni tricoxidesynthase(iNOS)-positive cells,and the protein expression levels of TH,cd11 b,p47-phox and iNOS in the substantia nigra(SN)of the midbrain of the mice in various groups were detected with immunohistochemistry,Western blotting and double-labeling immunofluorescence assay.Results Compared with control group,the mice in PD model group exhibited typical symptoms of PD,and the number of TH-positive cells and the protein expression level of TH in the substantia nigra of the mice in PD model group were reduced by about 45%and 50%;the number of cd11 b,p47-phox,iNOS-positive cells and the protein expression levels of cd11 b,p47-phox,iNOS were markedly increased(P0.01).Compared with PD model group,the symptoms of PD of the mice in tanshinoneⅡ A group were alleviated,the number of TH-positive cells and the expression level of TH protein in the SN were increased(P0.01),and the number of cd11 b,p47-phox and iNOS-positive cells and the TH protein expression levels were obviously decreased(P0.01).Conclusion Tanshinone ⅡA could mitigate the loss of dopaminergic neurons in the PD mouse model induced by MPTP.The mechanism of neuprotective effect may be related to the inhibition of microglial activation,NADPH oxidase and iNOS expressions.