含CpG基元核酸疫苗免疫慢性MPTP帕金森病小鼠的治疗作用

目的探讨含有CpG基元的α-突触核蛋白（α-synuclein，α-syn）核酸疫苗免疫慢性帕金森病小鼠的治疗效果。方法将本实验室成功构建的含有CpG基元的α-syn核酸疫苗-pVAX1-hα-Syn140用Qiagen试剂盒大量制备α-syn质粒；24只慢性MPTP帕金森病小鼠随机分为3组：实验组、空质粒对照组和PBS对照组，各组小鼠分别肌注pVAX1-hα-Syn140重组质粒、pVAX1空质粒和PBS各100μL，共免疫3次，每次间隔3周，末次免疫后2周，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-Syn140核酸疫苗免疫组小鼠的类帕金森病样症状与pVAX1空质粒和PBS对照组相比减轻，有显著差异（P〈0．01）；小鼠中脑黑质α-syn表达较对照组减少约39％（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46％～55％（P〈0．01）。结论pVAX1-hα-Syn140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。

Immunotherapeutic Effects of α-syn DNA Vaccine Containing CpG on Mouse with Parkinson's Disease

Objective To investigate the immunotherapeutic effects of a CpG-enhanced α-syn DNA vaccine on mice with Parkinson＇s disease. Methods The constructed α-syn DNA vaccine was injected intramuscularly to mice with Parkinson＇ s disease as the test group, the other two groups of mice were set up as control including vacant vector plasmid and PBS injected. The expression changes of α-syn and tyrosine hydroxylase （TH） in substantia nigra were visualized .by immunohistochemistry. The immmunotherapeutic effects in mice with Parkinson＇s disease were assessed by observing the behavioral changes in mice and the expression changes of α-syn and TH in substantia nigra. Results Immunization with α-syn DNA vaccine yielded an α-syn expression reduction rate of 39 % and an increase rate of 46% - 55 % of dopamine neuron counts, showing a significant difference compared with that of control groups （P〈0.01）. Conclusion The CpG-enhanced α-syn DNA vaccine have a better therapeutic effect on mice with Parkinson＇s disease.