多聚ADP-核糖聚合酶抑制剂对帕金森病小鼠相关脑区病理变化的影响

目的研究帕金森病(Park inson’s d isease,PD)小鼠黑质和纹状体多巴胺(dopam inergic,DA)能神经元数量和超微结构的变化及多聚ADP-核糖聚合酶(poly(ADP-ribose)polym erase,PARP)抑制剂PJ34的干预作用。方法采用1-甲基-4-苯-1,2,3,6-四氢吡啶(1-m ethyl-4-phenyl-1,2,3,6-tetrahydropyrid ine,MPTP)制备PD小鼠模型,并用PJ34进行干预,2h、24h、72h进行酪氨酸羟化酶(tyrosine hydroxylase,TH)免疫组化染色观察DA能神经元数量,透射电镜观察超微结构改变。结果与正常对照小鼠比较,PD小鼠黑质TH阳性神经元进行性减少,核膜皱缩,染色质凝聚成块并有边聚现象;纹状体TH阳性神经纤维稀疏,突触数量减少。与PD小鼠比较,PJ34干预组黑质TH阳性神经元明显增多,纹状体TH阳性神经纤维密度增加(P<0.01),细胞形态比模型组明显改善。结论PARP的活性改变在PD的发病过程中发挥重要作用,PARP抑制剂对DA能神经元有保护作用。

Pathological Changes in Specific Brain Regions of Mice with Parkinson's Disease and Effect of Poly(ADP-ribose) Polymerase Inhibitor

Objective To investigate the change of number and ultrastructure of dopaminergic(DA) neurons in substantia nigra and striatum of Parkinson's disease(PD) mice and the effect of poly(ADP-ribose) polymerase(PARP) inhibitor PJ34 on the neurons.Methods PD mice model was induced by abdominal injection of 1-methyl-4-phenylv1,2,3,6-tetrahydropyridine(MPTP),some mice were pretreated with PJ34.The dopamine neurons were stained by tyrosine hydroxylase(TH) immunohistochemistry at 2h,24h and 72h time point,the ultrastructural change was evaluated by transmission electron microscope.Results TH immunopositive cell bodies and fibers reduced gradually in the substantia nigra and striatum,the number of synapses and TH positive tibers in striatum were decreased compared with normal control.The nucleus membrane of dopaminergic neurons appeared shrinking and the chromatin showed agglutination with tendency of border agglutination in substantia nigra of PD mice.The number of cell bodies and fibers were increased in the substantia nigra and striatum(P<0.01) and the ultrastructural morphological changes were alleviated markly in the PJ34 pretreated group compared with PD mice.Conclusion The change of PARP activity takes an important role in PD pathogenesis,PARP inhibitor can protect dopamine neurons from injury.