Effect of Resveratrol on Motor Dysfunction in Unilateral 6-hydroxydopamine Parkinson's Model Ra

来源 :神经药理学报 | 被引量 : 0次 | 上传用户:strengthandhonor
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Objective:The present study was designed to investigate the effect of resveratrol (Res)on the motor function of Parkinsons model rats induced by 6-hydroxydopamine(6-OHDA)and to explore its underlying mechanism. Methods:After a week of adaptive feeding,50 male Sprague-Dawley(SD)rats were randomly divided into five groups:sham-operated group,normal group(Res, 30 mg·kg-1),model group(6-OHDA,8μg),6-OHDA+Res low-dose group(15 mg·kg-1,6-OHDA+Res high-dose group(30 mg·kg-1). 6-OHDA 8 μg(2 μg·μL-1)were injected into the substantia nigra of the rats to establish the model of dopaminergic neuronal damage,while the rats of sham group were injected with volume-matched saline with 0.2% Vitamin C.Rats were pretreated with Res for 1 day before 6-OHDA treatment. Model and sham groups were administered with volume-matched vehicle for 36 days.Rotarod test was applied to evaluate motor function of rats on 7 th,14 th and 21 th day after surgery,open field experiment and grid-walking test applied on 33 th and 35 th day,respectively. Then the rats were sacrificed.Immunohistochemistry was used to detect the number of TH-positive cells in substantia nigra pars compacta(SNc);the protein expression of TH,Bax,Bcl-2,pro-caspase-3, active-caspase-3,p-PDK1 and p-Akt in midbrain were detected by West blot. Results:The body weight,motor function,number of dopaminergic neurons in SNc and the protein expression of TH in midbrain of model group were significantly decreased compared with sham group;the protein of Akt phosphorylation levels were decreased while it showed no effect on PDK1,and the expression of apoptosis-related proteins Bax/Bcl-2,active-caspase-3 were significantly increased,pro-caspase-3 decreased. However,compared with model,the body weight,motor function,number of dopaminergic neurons in SNc and the protein expression of TH in midbrain of Res high-dose group were markedly increased;the protein of Akt phosphorylation levels were increased while it showed no effect on PDK1, the protein level of BDNF and TrkB were significantly decreased and the expression of apoptosis-related proteins Bax/Bcl-2,active-caspase-3 were significantly decreased,and pro-caspase-3 were increased.Conclusion:Under the experimental conditions,6-OHDA-induced motor dysfunction and apoptosis in dopaminergic neuronal cells of rats is significantly attenuated by Res,and its potential mechanism may be related to up-regulation of Akt phosphorylation at Ser473 and inhibit the expression of apoptosis-related proteins.
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