核酸疫苗免疫帕金森病小鼠加重黑质炎性反应

The immune inflammatory reaction of DNA vaccine in Parkinson's mouse

目的:探讨α-突触核蛋白(α-synuclein,α-syn)核酸疫苗免疫帕金森病小鼠后黑质免疫炎性反应的变化。方法:将本实验室成功构建的α-syn核酸疫苗-pVAX1-hα-Syn140用Qiagen试剂盒大量制备α-syn质粒;24只MPTP慢性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,观察小鼠中脑黑质CD11b和TNF-α表达变化。结果:pVAX1-hα-Syn140核酸疫苗免疫组小鼠中脑黑质CD11b表达较对照组增加约36%～37%(P<0.01);TNF-α表达较对照组增加约28%～32%(P<0.01)。结论:pVAX1-hα-Syn140核酸疫苗具有一定的炎性副反应,可在下一步的实验中进行优化,减轻其有害的细胞毒副反应。

Objective：To investigate the immune inflammatory reaction of the ha-syn DNA vaccine in Parkinson＇s mice. Methods： The constructed hα-syn DNA vaccine was injected intramuscularly to chronic Parkinson＇s mice three times at three-week interval as the test group. The other two groups of mice were set up as control, including vacant vector plasmids and PBS injected. The changes in expression of CD11b and TNF-α in substantia nigra were visualized two weeks after the third inoculation by immunohistochemistry. The immune inflammatory reactions in chronic Parkinson＇s mice were assessed by the changed expression of CD11 b and TNF-α in Substantia nigra. Results： Immunization with ha-syn DNA vaccine yielded increase of TNF-α expression and of activated microglia. The CD11b and TNF-α masculine expression of the test group increased by 36%-37% and 28%-32% respectively, showing a significant difference compared with those of control groups. Conclusion： hα-syn DNA vaccine can aggravate immune inflammatory reaction in chronic Parkinson＇ s mice in some degree.