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目的:研究神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methy-4-phenyl-1,2,3,6-tetrahy-dropyridine,MPTP)对小鼠脑内星形胶质细胞及肿瘤坏死因子-α(Tunlornecrosis factor alpha,TNF-α)的影响,了解MPTP致帕金森病发病机制。方法:将神经毒素MPTP注入C57BL/6小鼠腹腔内,制备帕金森病动物模型。观察注药后小鼠行为学变化,免疫组化检测各时间点多巴胺能神经元缺失和星形胶质细胞增生与激活情况,以及TNF-α表达水平的变化。结果:MPTP组黑质多巴胺(dopamine,DA)能神经元的数量随注射天数增加而持续减少,星形胶质细胞数量明显增高,GFAP及TNF-α在模型组黑质内有中强阳性表达,与对照组相比差异有统计学意义(P<0.05)。结论:MPTP可诱导星形胶质细胞的激活和增生,启动脑内炎症反应而介导DA神经元死亡。
Objective: To investigate the effect of 1-methy-4-phenyl-1,2,3,6-tetrahy-dropyridine (MPTP) To study the effect of MPTP on the pathogenesis of Parkinson’s disease in mice and the effect of astrocyte and tumor necrosis factor-alpha (TNF-α) in mice brain. Methods: MPTP was injected into C57BL / 6 mice intraperitoneally to prepare animal model of Parkinson’s disease. The behavioral changes of mice after injection were observed. Immunohistochemistry was used to detect the loss of dopaminergic neurons and the proliferation and activation of astrocytes at various time points, as well as the changes of TNF-α expression. Results: The number of dopaminergic neurons in the substantia nigra of MPTP decreased continuously with the increase of injection days, and the number of astrocytes was significantly increased. The positive expression of GFAP and TNF-α in substantia nigra of model group , Compared with the control group, the difference was statistically significant (P <0.05). Conclusion: MPTP can induce the activation and proliferation of astrocytes and initiate the inflammatory reaction in the brain to induce the death of DA neurons.