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目的:探讨MPTP(1-甲基-4-苯基-1,2,3,6-四氢吡啶)对快速老化小鼠(senescence accelerated mouse prone8,SAMP-8)黑质纹状体系统的急性损害及小胶质细胞激活与损害的关系。方法:57只健康雄性12周龄SAMP8小鼠,随机分为生理盐水对照组和MPTP组,每组再分别于第1次给药后6h、24h、3d和8d四个时间点处死小鼠,每个时间点6～9只。SAMP8小鼠背部皮下注射MPTP20mg·kg-1,1次/2h,注射4次,观察各时间点小鼠的自主活动;免疫组织化学染色检测各时间点黑质TH+神经元数量、纹状体TH免疫反应性及小胶质细胞的状态;HPLC技术检测纹状体DA含量。结果:第3次注射后小鼠出现明显活动减少,并于第1次给药后48h恢复近正常水平。与对照组相比:MPTP组黑质TH+神经元数目于第1次注射后6h、24h、3d、8d分别减少7.06%(P=0.235)、12.79%(P<0.05)、22.49%(P<0.01)、42.39%(P<0.001),两个时间点之间比较3d与8d有统计学差异(P<0.05);与对照组相比,MPTP组纹状体TH免疫反应性(COD值)减低,6h(P<0.05)、24h(P<0.01)、3d(P<0.001)、8d(P<0.001),两个时间点之间比较24h与3d比较差异有统计学意义(P<0.05);纹状体多巴胺含量6h降低79.09%(P<0.001),24h降低80.3%(P<0.001),3d降低86.6%(P<0.001),8d降低81.0%(P<0.001),但24h、3d、8d比较无统计学差异。纹状体小胶质细胞于给药后24h免疫反应性明显增强,3d明显激活,8d激活现象明显回落。结论:MPTP可导致SAMP8小鼠黑质纹状体系统的急性损害,出现自主活动减少、黑质多巴胺能神经元减少及纹状体多巴胺能纤维脱失,多巴胺含量降低;小胶质细胞激活可能与MPTP-SAMP8小鼠的黑质纹状体系统损伤有关。
OBJECTIVE: To investigate the acute effects of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) on nigrostriatal system in senescence accelerated mouse prone8 (SAMP-8) Damage and the relationship between microglial activation and damage. Methods: Fifty-seven healthy male 12-week-old SAMP8 mice were randomly divided into saline control group and MPTP group. Each group was sacrificed at 6h, 24h, 3d and 8d after the first administration, Each time point 6 to 9 only. SAMP8 mice were injected subcutaneously with MPTP 20 mg · kg -1,1 times / 2 hours on the back of the mice to observe the autonomic activity of mice at each time point. The number of substantia nigra TH + neurons, Immunoreactivity and the status of microglial cells were detected by HPLC. Results: After the third injection, there was a significant decrease in the activity of the mice and returned to normal levels 48h after the first administration. Compared with the control group, the number of TH + neurons in substantia nigra in MPTP group decreased by 7.06% (P = 0.235), 12.79% (P <0.05) and 22.49% at 6h, 24h, 3d and 8d after the first injection respectively 0.01) and 42.39% (P <0.001). There was a significant difference between 3d and 8d (P <0.05) between the two time points. Compared with the control group, TH immunoreactivity (COD) (P <0.05), 24h (P <0.01), 3d (P <0.001), 8d (P <0.001), there was significant difference between the two time points ), Striatum dopamine content decreased 79.09% (P <0.001) at 6h, 80.3% at 24h (P <0.001), 86.6% at 3d (P <0.001) and 81.0% 3d, 8d no statistical difference. Striatum microglia 24h after administration of immunoreactivity was significantly enhanced 3d was activated, 8d activation was significantly reduced. CONCLUSION: MPTP can cause acute damage to nigrostriatal system in SAMP8 mice, with decreased autonomic activity, decreased substantia nigra dopaminergic neurons and striatal dopaminergic fibers with loss of dopamine content and microglial activation And MPTP-SAMP8 mice nigrostriatal system damage.