Neuroprotective rather than neurorescue or neurorestorative effect of selegiline against MPTP-induced dopaminergic toxicity

目的：研究司来吉兰（ｓｅｌｅｇｉｌｉｎｅ，Ｓｅｌ）的神经保护作用及其对单胺氧化酶Ｂ（ＭＡＯＢ）的抑制作用．方法：高效液相电化学检测法测定小鼠纹状体内多巴胺（ＤＡ）及其代谢产物的含量．荧光检测法测定小鼠脑ＭＡＯＢ的活性．结果：ＭＰＴＰ（３０ｍｇ·ｋｇ－１ｉｐ）明显减少小鼠纹状体内ＤＡ含量（７３％）．预先给予Ｓｅｌ（１０ｍｇ·ｋｇ－１ｉｐ）可以阻断ＭＰＴＰ的神经毒性；而ＭＰＴＰ损伤后再给予Ｓｅｌ则否．ＭＰＴＰ损伤后２ｗｋ内，Ｓｅｌ对纹状体ＤＡ水平的自然恢复无促进作用．ＭＰＰ＋外周给药无神经毒性．Ｓｅｌ对小鼠脑内ＭＡＯＢ有明显抑制作用（ＩＣ５０＝３８；９５％可信限为：３１－４５μｇ·Ｌ－１）．结论：Ｓｅｌ具有与其抑制脑内ＭＡＯＢ活性相关的对抗ＭＰＴＰ毒性的神经保护作用．

AIM: To study the neuroprotective, neuro￣rescue, neuro￣restorative effects of selegiline (Sel) on nigrostriatal dopaminergic neuronal system and its inhibition of brain monoamine oxidase B (MAO B). METHODS: The striatal levels of dopamine and its metabolites were measured using HPLC with electrochemical detection (HPLC EC). The inhibition of MAO B was tested by an improved fluorimetric assay. RESULTS: 1 Methyl 4 phenyl 1,2,3,6 tetra hydro pyridine (MPTP) (30 mg·kg -1 ip) reduced the striatal dopamine level by 73 % in mice. Selegiline (Sel, 10 mg·kg -1 ip ) before, but not after, MPTP treatment protected against MPTP induced nigrostriatal dopaminergic neurotoxicity. There were no differential effects between Sel and saline treatments on the recovery of striatal dopamine levels, which were partially restored during 2 wk. 1 Methyl 4 phenyl￣pyri￣dinium (MPP +) (5 mg·kg -1 ip) produced no dopaminergic neurotoxicity. Furthermore, Sel selectively and irreversibly inhibited mouse brain MAO B in vitro (IC 50 =17 nmol·L -1 , 95 % confidence limits=14-20 nmol·L -1 ). CONCLUSION: Selegiline has neuroprotective rather than neurorescue or neurorestorative effects on MPTP induced nigrostriatal dopaminergic neuronal degeneration, which is directly pertinent to its selective and irreversible inhibition of brain MAO B activity.