尼克酰胺对帕金森病模型小鼠的保护作用

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。

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

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(P<0.01),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(P<0.01) and showed no significant difference compared to controls(P>0.05).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.