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目的探讨预防注射优化hα-syn基因疫苗对多巴胺神经元在遭受急性神经毒素损害时的保护作用。方法在小鼠双侧后肢胫骨前肌部位分别注射优化基因疫苗、空重组质粒或PBS各50μl,共3次。末次注射3周后,优化基因疫苗组皮下注射MPTP30mg/kg,对照组用等容量的PBS背部皮下注射,每日1次,连续5d。最后1次模型注射后,观察行为学和病理生理改变。结果优化基因疫苗组小鼠的爬杆分数与空重组质粒组比较明显减少(P<0.05),与PBS对照组比较,爬杆分数增多,但差异无统计学意义(P>0.05)。优化基因疫苗组与空重组质粒组相比,黑质区酪氨酸羟化酶阳性细胞数明显增多,凋亡细胞数明显减少(P<0.05),α-突触核蛋白表达略减少(P>0.05)。空重组质粒组与PBS对照组相比,黑质区酪氨酸羟化酶阳性细胞数明显减少,凋亡细胞明显增多(P<0.05),α-突触核蛋白表达明显增多(P<0.05)。结论优化hα-syn基因疫苗预防注射能够较好的防止神经毒素对黑质多巴胺细胞的损害,对多巴胺神经细胞具有保护作用。
Objective To investigate the protective effect of preventive injection of hα-syn gene vaccine against dopamine neurons in acute neurotoxin damage. Methods Optimized gene vaccines, empty recombinant plasmids or PBS 50μl were injected into the anterior tibialis anterior muscle of bilateral hind limbs in mice for 3 times. Three weeks after the last injection, MPTP was administered subcutaneously at a dose of 30 mg / kg in the gene vaccine group, while the control group was injected subcutaneously with PBS of the same volume once daily for 5 days. After the last injection of the model, behavioral and pathophysiological changes were observed. Results The score of climbing pole in the optimized vaccine group was significantly decreased compared with the empty plasmid group (P <0.05). Compared with the PBS control group, the score of climbing pole increased, but the difference was not statistically significant (P> 0.05). Compared with the empty plasmid group, the number of tyrosine hydroxylase positive cells in substantia nigra was significantly increased, the number of apoptotic cells was significantly decreased (P <0.05), and the expression of α-synuclein was slightly reduced (P > 0.05). Compared with PBS control group, the number of tyrosine hydroxylase positive cells in nigral area was significantly decreased, the number of apoptotic cells was significantly increased (P <0.05) and the expression of α-synuclein was significantly increased in empty plasmid group ). Conclusion The optimized hα-syn gene vaccine can prevent the neurotoxin from damaging the substantia nigra dopamine cells and protect the dopaminergic neurons.