摘要目的　探讨MPTP和MPP+对黑质多巴胺能神经元和PC12细胞的凋亡的作用及咪多吡(Eldepryl)对MPTP的拮抗作用。方法　应用MPTP腹腔注射C57-BL小鼠及口服Eldepryl预处理,分别用TUNEL法和FACS法对黑质神经元进行凋亡检测; 体外实验用同样的方法对分别加入MPP+、MPTP或PBS的PC12细胞进行凋亡检测。 结果　MPTP 30mg/kg连续注射7天能诱致的黑质神经元凋亡,Eldepryl预处理能完全拮抗MPTP诱致黑质神经元凋亡; MPP+能使PC12细胞发生凋亡，而MPTP则不能导致PC12细胞凋亡。结论　MPTP可能通过细胞凋亡机制导致黑质神经元死亡,其凋亡作用是通过MPTP代谢转化为MPP+而实现的，Eldepryl能抑制MPTP向MPP+的转化，从而有效地拮抗MPTP诱致黑质神经元凋亡。

abstractsObjective　To study the apoptotic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the nigral dopaminergic neurons of mice and 1-methyl-4-phenylpyridium ion (MPP+) on pheochromocytoma (PC12) cells, as well as the antagonism of Eldepryl against MPTP's apoptotic effect.Methods　Three groups of C57BL mice were treated with MPTP, Eldepryl plus MPTP and normal saline, respectively, for 7 days before performing TUNEL (terminal deoxyneucleotidyl transferase-mediated dUTP-x nick end labeling) and FACS (fluorescence activated cell sorting) analyses of neuronal apoptosis in the substantia nigra. The same tests were employed in cell culture to examine apoptosis in PC12 cells treated with MPP+, MPTP or PBS. Results　Intraperitoneal administration of MPTP 30*!mg/kg could induce nigral apoptosis, and oral use of Eldepryl prior to MPTP treatment could completely prevent the nigral apoptosis caused by MPTP. MPP+, an intermediate metabolite of MPTP, could lead to the apoptosis of PC12 cells, whereas MPTP itself had no such effect on PC12 cells.Conclusions　The experiment indicated that the neurotoxin, MPTP, might cause the death of nigral neurons through a mechanism of apoptosis and this effect might be mediated by its bioactive intermediate metabolite MPP+. Eldepryl could protect the neurotoxicity from MPTP.