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目的探索预防注射p VAX1-IL-4/SYN-B核酸疫苗对1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)诱导的慢性帕金森病模型小鼠纹状体神经营养因子表达的影响,进一步探讨核酸疫苗神经保护作用的具体机制。方法 48只C57BL/6雄性小鼠完全随机分为4组:正常对照组、空质粒组、PBS组和核酸疫苗组,每组12只;分别肌注PBS、空质粒、PBS和p VAX1-IL-4/SYN-B核酸疫苗,然后给予后3组小鼠注射MPTP建立慢性帕金森病模型。采用自由活动实验观察小鼠行为学变化;Western blot、免疫组化检测纹状体区酪氨酸羟化酶(tyrosine hydroxylase,TH)表达;Western blot检测小鼠纹状体胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)、脑源性神经营养因子(brain derived neurotrophic factor,BDNF)表达。结果与PBS组和空质粒组比较,核酸疫苗组小鼠运动迟缓症状明显改善(P<0.05),纹状体区GDNF、BDNF表达升高(P<0.05),TH丢失明显减少(P<0.05)。结论 p VAX1-IL-4/SYN-B核酸疫苗预防免疫可增加慢性MPTP帕金森病模型小鼠纹状体区神经营养因子表达,具有一定的神经保护作用。
Objective To explore the preventive effect of p VAX1-IL-4 / SYN-B DNA vaccine against 1-methyl-4-phenyl-1,2 , 3,6-tetrahydropyridine (MPTP) on the expression of neurotrophin of striatum in mice with chronic Parkinson’s disease and to further explore the specific mechanism of the neuroprotective effect of nucleic acid vaccine. Methods 48 C57BL / 6 male mice were randomly divided into 4 groups: normal control group, empty plasmid group, PBS group and nucleic acid vaccine group, 12 mice in each group; intramuscular injection of PBS, empty plasmid, PBS and p VAX1-IL -4 / SYN-B nucleic acid vaccine, and then given 3 mice after injection of MPTP to establish a chronic Parkinson’s disease model. The behavioral changes of mice were observed by free-moving test. The expression of tyrosine hydroxylase (TH) in the striatum was detected by Western blot and immunohistochemistry. The expression of glial cell line-derived neurons Glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). Results Compared with PBS group and empty plasmid group, the mice with nucleic acid vaccine showed significant improvement of motor symptoms (P <0.05), the expression of GDNF and BDNF in striatum increased (P <0.05), and the loss of TH decreased significantly (P <0.05 ). CONCLUSION: Vaccination with p VAX1-IL-4 / SYN-B DNA vaccine can increase the expression of neurotrophic factor in striatum of mice with chronic MPTP-induced Parkinson’s disease and has certain neuroprotective effect.