摘要
目的:利用动物模型探讨死亡相关蛋白(FADD)小分子干扰RNA(siRNA)对帕金森病(PD)大鼠黑质酪氨酸羟化酶(TH)表达的影响。方法:40只雄性Wistar大鼠随机分为4组。经立体定向定位黑质,PD组:注入6-羟基多巴(6-OHDA);siRNA组:注入FADD siRNA2次后再注入6-OHDA;SiRNA阴性对照组:注入FADD siRNA阴性对照物2次后再注入6-OHDA;正常对照组:注入抗坏血酸生理盐水。各组大鼠术后4周处死,取鼠的术侧中脑黑质,利用原位杂交检测FADD、TH mRNA表达。结果:PD组与正常对照组比较FADD mRNA表达显著增加(P<0.01);siRNA组与PD组比较FADD mRNA表达显著减少(P<0.05);siRNA阴性对照组与正常对照组比较FADD mRNA表达量无显著差异(P>0.05)。PD组与正常对照组比较TH mRNA表达显著减少(P<0.01);siRNA组与PD组比较TH mRNA表达显著增加(P<0.05);siRNA阴性对照组与正常对照组比较TH mRNA表达量差异无统计学意义(P>0.05)。结论:FADDsiRNA可能通过抑制凋亡对PD大鼠模型有一定的保护和治疗作用。
Aim:To explore the effect of Fas-associated death domain(FADD) siRNA on tyrosine hydroxylase (TH) on Parkinson's disease modal.Methods:A total of 40 male Wistar rats were randomly assigned to four groups,10 rats in each group.Ten rats in PD group were prepared to be hemiparkinsonian models induced by unilateral stereotaxic infusion of 6-hydroxydopamine(6-OHDA) in right substantia nigra of midbrain.FADD siRNA sequences in FADD siRNA group were separately injected into the right substantia nigra of siRNA,then infusion of 6-OHDA.siRNA negative control sequences in siRNA negative control groups were separately injected into the right substantia nigra of siRNA,and then infusion of 6-OHDA.The rats in the control group were treated with a mixture of ascorbic acid and normal saline.Four weeks after operation,the expression of FADD and TH mRNA in the right substantia nigra through in situ hybridization were compared.Results:Compared with the normal group,the expression of FADD mRNA in PD significantly increased.Compared with PD group,the expression of FADD mRNA in FADD SiRNA group significantly decreased.Compared with the normal group, the expression of TH mRNA in PD significantly decreased.Compared with PD group,the expression of TH in FADD siRNA group significantly increased.Conclusion:FADD siRNA may protect and therapy PD rats by inhibiting DA neuron apoptosis and improving TH mRNA expression.
出处
《中国临床神经科学》
2011年第2期150-154,共5页
Chinese Journal of Clinical Neurosciences