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目的探讨1-甲基-4-苯基-1、2、3、6-四氢吡啶(1-Methyl-4-Phenyl-1,2,3,6-etrahydropyridine,MPTP)对不同年龄快速老化小鼠SAMP8(senescence-accelerated mouse prone8)黑质纹状体系统的急性损害,揭示衰老在帕金森病(Parkinson s disease,PD)发病中的作用。方法雄性12、24周龄SAMP8小鼠,各随机分为盐水组和MPTP组,于第1次给药后6h、24h、3d和8d处死小鼠。背部皮下注射MPTP20mg.kg-1,每2h1次,注射4次;观察各时间点小鼠的自主活动,黑质TH+神经元数量,纹状体TH免疫反应性,纹状体DA含量的变化。结果12周龄小鼠自主活动减少于第1次给药后48h恢复近正常水平;24周龄小鼠至7d时日仍没有恢复近正常水平。12周龄小鼠黑质TH+神经元数目于第1次注射后6h、24h、3d、8d分别减少7.06%,12.79%,22.49%,42.39%;24周龄小鼠分别减少14.23%,23.85%,36.77%,45.9%。纹状体TH免疫反应性COD值,24周龄小鼠在MPTP后24h,3d较12周龄小鼠明显降低(P<0.05)。12周龄小鼠纹状体多巴胺含量各时间点分别降低79.09%,80.33%,83.86%,80.14%;24周龄小鼠分别降低79.70%,86.64%,75.20%,92.32%,但两个周龄之间无统计学差异。结论证实MPTP可导致SAMP8小鼠黑质纹状体系统损害,老龄鼠黑质纹状体的损伤更严重。
Objective To investigate the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Acute impairment of the nigrostriatal system in senescence-accelerated mouse prone8 cells reveals the role of aging in the pathogenesis of Parkinson’s disease (PD). Methods Male 12 and 24-week-old SAMP8 mice were randomly divided into saline group and MPTP group. Mice were sacrificed at 6h, 24h, 3d and 8d after the first administration. Mice were injected subcutaneously with MPTP 20mg.kg-1 every 2 hours for four times. The changes of autonomic activity, the number of TH + neurons in substantia nigra, the TH immunoreactivity in striatum and the content of DA in striatum were observed. Results The autonomic activity of 12-week-old mice decreased to nearly normal level at 48h after the first administration. The normal level was not restored to the normal level on the 7th day after 24-week-old mice. The number of TH + neurons in substantia nigra of 12-week-old mice decreased by 7.06%, 12.79%, 22.49% and 42.39% at 6h, 24h, 3d and 8d after the first injection respectively. The 24-week old mice decreased by 14.23% and 23.85% , 36.77%, 45.9%. Thyroid TH immunoreactive COD values in 24-week-old mice were significantly lower than those of 12-week-old mice at 24 and 3 days after MPTP (P <0.05). The striatum dopamine content in mice of 12 weeks old decreased by 79.09%, 80.33%, 83.86% and 80.14%, respectively. The mice in 24 weeks old decreased 79.70%, 86.64%, 75.20% and 92.32% There was no significant difference between the ages. Conclusions MPTP can cause the damage of nigrostriatal system in SAMP8 mice and the nigrostriatal damage in the aged rats.