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目的探讨α-突触核蛋白(α-synuclein,α-syn)核酸疫苗免疫对MPTP慢性帕金森病(PD)小鼠的治疗效果。方法将该实验室成功构建的α-syn核酸疫苗-pVAX1-hα-Syn84-140用Qiagen试剂盒大量制备α-syn质粒;24只MPTP慢性PD小鼠随机分为3组:疫苗组、空质粒对照组和PBS对照组,各组小鼠分别肌注pVAX1-hα-Syn84-140重组质粒,pVAX1空质粒和PBS各100μl,共免疫3次,每次间隔3w,末次免疫后2w,观察小鼠行为学变化及中脑黑质α-syn表达和多巴胺能神经元数目变化。结果pVAX1-hα-Syn84-140核酸疫苗免疫组小鼠的类PD样症状与空质粒和PBS对照组相比显著减轻(P<0.01);小鼠中脑黑质α-syn表达较对照组减少约30%(P<0.01),且多巴胺能神经元数目较空质粒和PBS对照组增多了31%～39%(P<0.01)。结论pVAX1-hα-Syn84-140核酸疫苗具有较强的免疫原性,能对帕金森病小鼠产生较好的免疫治疗作用。
Objective To investigate the therapeutic effect of α-synuclein (α-syn) DNA vaccine on MPTP chronic Parkinson’s disease (PD) mice. Methodsα-syn plasmids were successfully prepared from α-syn DNA vaccine-pVAX1-hα-Syn84-140 successfully constructed by the laboratory using Qiagen kit. 24 MPTP chronic PD mice were randomly divided into 3 groups: Vaccine group, empty plasmid The mice in each group were intramuscularly injected with recombinant plasmid pVAX1-hα-Syn84-140, empty plasmid pVAX1 and PBS, respectively. The mice were co-immunized three times with an interval of 3 weeks and 2 weeks after the last immunization. The mice were observed Behavioral changes and midbrain substantia nigra α-syn expression and changes in the number of dopaminergic neurons. Results The PD-like symptoms in mice vaccinated with pVAX1-hα-Syn84-140 were significantly reduced compared with the empty plasmid and the PBS control group (P <0.01). The expression of α-syn in the midbrain substantia nigra was decreased About 30% (P <0.01). The number of dopaminergic neurons increased by 31% -39% (P <0.01) compared with empty plasmid and PBS control group. Conclusion The pVAX1-hα-Syn84-140 DNA vaccine has strong immunogenicity and can produce good immunotherapy effects on mice with Parkinson’s disease.