The Effect Of Synphilin-1 SiRNA On The Expression Of SOD1, α-synuclein In The Rat Model Of Parkinson's Disease Induced By 6-hydroxydopamine

Objective To explore the role of synphilin-1 in the pathogenesis of Parkinson's disease,we investigated the effect of synphilin-1 siRNA on the expressions ofα-synuclein,SOD1,TH in substantia nigra in rat model of Parkinson disease(PD) induced by 6-hydroxydopamine.Methods 60 healthy male Wistar rats were devided into four groups randomly,PD model group(n=10),siRNA group(n=10),siRNA negative control group(n=10),the sham operation group(n=10).For the PD model group:6-OHDA(18μg/3μl) containing 0.2 mg/ml 1-ascorbic acid was stereotaxically injected in the left substantia nigra at the rate 1μg /min.siRNA group:According to the product's instruction,1nmol/3μl synphilin-1siRNA was stereotaxically injected in the left substantia nigra twice,and then 6-OHDA was stereotaxically injected in the left substantia nigra with the sane method as the model group.Other managements of the sham-operated group were exactly same as the model group,siRNA negative control group:Except for injection of same amount of synphilin-1 negative control siRNA,other managements of the siRNA negative control group were exactly same as the siRNA group.The sham operation group:Except for injection of same amount of normal saline containing 0.2 g/L antiscorbic acid,other managements were exactly same as the model group.The rats were given water and food intake freely for three weeks.The rats were decapitated and brains were removed immediately.The expressions of synphilin-1,α-synuclein,SOD1,TH were detected by immunohistochemistry and in situ hybridization.Results:Compared to the PD model group,the expressions of Synphilin-1,α-synuclein in siRNA group significantly decreased;Compared to the the sham operation group,the expressions of Synphilin-1,α-synuclein and TH in siRNA group have no significant difference(p＞0.05);Compared to the the PD group,the expressions of Synphilin-1,α-synuclein,and TH in siRNA negative control group have no significant difference(p＞0.05);Conclusions:Synphilin-1siRNA can significantly suppress the expression of Synphilin-1.The expression of SOD1,TH andα-synuclein can be reversed by Synphilin-1 siRNA,which indicated that synphilin-1siRNA may have a neuroprotective effect against substantia nigra neurons damage induced by 6-OHDA.These protective properties might be,at least in part,via regulating the expressions ofα-synuclein,SOD1.