1-甲基-4-苯基-1,2,3,6-四氢吡啶致快速老化小鼠模型黑质纹状体系统的形态学改变

Morphologic change of nigra and striatum system of senescence accelerated mouse prone 8 induced by MPTP

目的探讨1-甲基-4-苯基-1,2,3,6四氢吡啶(MPTP)导致快速老化小鼠(SAMP8)黑质纹状体系统的形态学改变。方法24只健康雄性12周龄SAMP8小鼠,随机分为盐水对照组和MPTP组,分别于第一次给药后6、24h、3和8d4个时间点处死小鼠,每个时间点3只;背部皮下注射MPTP20mg/kg,每2h一次,注射4次。用免疫组织化学染色技术检测各时间点黒质酪氨酸羟化酶(TH)阳性神经元形态及数量、纹状体TH免疫反应性及黑质区尼氏染色检测神经元状态。结果MPTP组和对照组比较:黑质TH阳性神经元数目于第1次注射后6、24h、3、8d分别减少7.06%(P>0.05),12.79%(P<0.05),22.49%(P<0.01),42.39%(P<0.001),其中3d和8d比较有显著差异(P<0.01);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),其中24h与3d比较差异显著(P<0.05);尼氏染色可见对照组细胞多,形态完整,胞核饱满,核仁清晰,尼氏体丰富。MPTP注射后逐渐出现细胞胞核固缩,核仁模糊不清,胞体及胞核形态不规则,崩解,细胞稀疏,残存的细胞周围可见大量细胞碎片。结论MPTP可导致SAMP8小鼠黑质多巴胺(DA)能神经元减少及纹状体DA能纤维丢失等帕金森样病理改变。

Objective To explore the morphologic change of nigra and striatum system of senescence accelerated mouse prone8（SAMP8） induced by MPTP.Methods 24 SAMP8 mice of 12 weeks old were randomly divided into physiological saline control group and MPTP group.The mice were killed on 6,24 h,3,8 d after the first given medicine respectively（n=3）.MPTP was given by backside hypodermic injection on 20 mg·kg-1·2 h-1,and added up 4 times.Tyrosine（TH） positive cells in nigra TH immune reactivity in striatum were observed by immunohistochemistry and the morphologic changes of neurons in nigra were observed by Nissl＇s staining.Results Compared with control group,the TH positive cells in nigra decreased by 7.06%（P=0.235）,12.79%（P〈0.05）,22.49%（P〈0.01）,42.39%（P〈0.001）on 6,24 h,3,8 d after the first given medicine respectively,and there was obvious difference between the 3 and 8 days after the first given medicine（P〈0.01） in MPTP group.Compared with control group,TH immune reactivity in striatum decreased in MPTP group,and there was obvious difference between the 24 h and 3 days after the first given medicine（P〈0.05）.In control group,Nissl＇s positive cells was much more,had integrated morphology,full and clear nucleolus and full Nissl＇s bodies.After given MPTP,there were karyopyknosis and ambiguous nucleolus,irregular sharp cell body and nucleolus,disintergration,and amount of cell debris.Conclusions MPTP can decrease the dopamine energy neurons in nigra and dopamine energy nerve fiber in striatum,induce the pathologic changes of Parkinson disease（PD）,which provide theory basis on the application of SAMP8 mice for the PD research.