尼克酰胺对帕金森病模型小鼠的保护作用

Protective effect of nicotinamide in a mouse Parkinson′s disease model

目的:观察尼克酰胺对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱发的小鼠帕金森病(PD)模型中多巴胺能神经元的保护作用,并初步探讨其可能的作用机制。方法:在MPTP(每天30mg/kg×5 d,i.p.)注射前1h腹腔注射尼克酰胺(500 mg/kg),最后1次注射后5天观察小鼠运动能力的改变,检测纹状体多巴胺含量,并分析小鼠全脑及纹状体中乳酸脱氢酶(LDH)及一氧化氮合酶(NOS)的活性变化。结果:1)尼克酰胺能显著改善MPTP小鼠的自主运动能力(P<0.01),但对游泳、爬杆和悬挂等行为没有显著影响;2)尼克酰胺能显著减轻MPTP诱发的纹状体多巴胺含量的降低(P<0.01);3)全脑的LDH和NOS活性在各组之间没有显著差别,但纹状体的LDH和NOS活性在MPTP处理的小鼠中显著升高(P<0.01),尼克酰胺能显著降低MPTP引起的LDH和NOS活性升高(P<0.01),并且与对照组相比没有显著区别(P>0.05)。结论:尼克酰胺可以有效减轻MPTP诱发的帕金森病小鼠模型中多巴胺能神经元的损伤,这种保护作用可能与降低神经元的坏死和抑制NOS活性有关。

Objective： To examine the protective effect of nicotinamide on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced Parkinson′s disease（PD） in mouse model and its mechanisms.Methods： Parkinson′s disease was induced by injection of MPTP in adult male C57BL/6 mice,nicotinamide（500 mg/kg,i.p.） was given prior to subacute（30 mg/kg/d×5 d,i.p.） MPTP administration.Locomotor activities,striatal dopamine levels,lactate dehydrogenase（LDH） and NO synthase（NOS） activities of whole brains and striatum were analyzed at d5 after last MPTP injections.Results： Pretreatment with nicotinamide significantly improved the locomotor activity in the open-field test（P0.01）,but not in the swimming test and grip climbing test.Nicotinamide administration resulted in sparing striatal dopamine levels from MPTP-induced dopamine depletion.There was no significant difference in LDH and NOS activities in the whole brains among the groups;but the activities in the striatum were drastically elevated after MPTP treatment.Nicotinamide pretreatment markedly inhibited MPTP-induced LDH and NOS activities（P0.01） and showed no significant difference compared to controls（P0.05）.Conclusion： Nicotinamide protects dopaminergic neurons against MPTP-induced neurodegeneration,which suggests that the neuroprotective effects be associated with the inhibition of cell injuries and NOS activities.