帕金森病相关研究

Objective:The present study was designed to investigate the effect of resveratrol (Res) on the motor function of Parkinson’s 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 fi ve groups:sham-operated group,normal group (Res,30 mg·kg-1),model group (6-OHDA,8 μg),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 fi eld 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 Western 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 signifi cantly decreased and the expression of apoptosis-related proteins Bax/Bcl-2,active-caspase-3 were significantly decreased,and pro-caspase-3 were increased.