尼古丁对MPTPPD小鼠纹状体NOS活性的影响  

Influence of nicotine on the striatum NOS activity in MPTP-PD mice

作　　者：陈涛[1] 唐北沙[1] 单桂珍 庞英华[1] 严新翔[1] 柳四新[1] 李昌琪[3] 梁静慧[1] 许宏伟[1] 

机构地区：[1]中南大学湘雅医院神经内科,湖南长沙410008 [2]衡阳市核工业415医院神经内科,湖南衡阳421002 [3]中南大学湘雅医学院神经生物学研究室,湖南长沙410008

出　　处：《中国神经科学杂志》2002年第2期547-550,共4页

基　　金：湖南省科委基金 (10 13 1)

摘　　要：为观察帕金森病 (Parkinsondisease,PD)模型小鼠脑组织中一氧化氮合酶 (NOS)活性的变化 ,研究尼古丁在PD中的可能作用机制。本实验采用 1 甲基 4 苯基 1,2 ,3,6 四氢吡啶 (MPTP)建立C5 7BL小鼠PD模型 ,分别应用比色分析、高效液相色谱 电化学以及免疫组织化学检测MPTP和尼古丁对C5 7BL小鼠纹状体NOS活性 ,多巴胺 (DA)、二羟基苯乙酸 (DOPAC)、高香草酸 (HVA)水平及酪氨酸羟化酶 (TH)、神经元型一氧化氮合酶(nNOS)免疫组化的影响。结果发现尼古丁能明显抑制MPTP引起的NOS活性增加 (每mg蛋白质分别为 15 .6 3IU± 1.5IU和 13.0 9IU± 0 .89IU ,P <0 .0 1)及nNOS阳性神经元的数量 (分别为 6 8.6 1± 3.84和 39.2 6± 2 .6 4,P <0 .0 1) ,并能明显减轻MPTP引起的小鼠纹状体DA(每g脑组织中分别为 0 .73μg± 0 .2 8μg和 1.4 0 μg± 0 .19μg ,P <0 .0 1)、DOPAC(每g脑组织中分别为 0 .4 1μg± 0 .13μg和 0 .90 μg± 0 .0 9μg ,P <0 .0 1)、HVA(分别为0 .31μg± 0 .0 7μg和 0 .4 7μg± 0 .19μg ,P <0 .0 1)的降低及TH阳性神经纤维的损害。因此认为 ,尼古丁可能通过抑制nNOS的活性而对MPTP的神经毒性具有保护作用。In this study we have investigated the influence of nicotine on nitric oxide synthase (NOS) activity in the striatum of 1 methyl 4 phenyl 1,2,3,6 tetrahydropyridine (MPTP) induced Parkinson disease (PD) model of C57BL mice. The effects of MPTP and nicotine on NOS activity,on levels of dopamine (DA), 3,4 dihydroxyphenlacetic acid (DOPAC), hemovanillic acid (HVA) ,and on tyrosine hydroxylase (TH)postive nerve fibres and neuron nitric oxide synthase(nNOS) postive neurons were measured by using colorimetic analysis, HPLC with electrochemical detection, and immunohistochemical analysis. NOS activity in the striatum of MPTP treated C57BL mice was significantly higher than the control mice. Nicotine might inhibit the increased NOS activity (15.63 IU±1.5 IU vs 13.09 IU±0.89 IU;per mg of protein, P< 0.01) and nNOS postive neurons (68.61±3.84 vs 39.26±2.64, P< 0.01). Nicotine significantly attenuated MPTP induced depletions of striatal DA (0.73 μg±0.28 μg vs 1.40 μg±0.19 μg,per g of the striatum, P< 0.01),DOPAC(0.41 μg±0.13 μg vs 0.90 μg±0.09 μg,per g of the striatum, P< 0.01),HVA (0.31 μg±0.07 μg vs 0.47 μg±0.19 μg,per g of the striatum, P< 0.01) and the destruction of TH postive nerve fibres. We concluded nicotine may protect C57BL mice against MPTP induced dopaminergic neurotoxicity by inhibiting nNOS activity. \[

关 键 词：尼古丁 MPTP-PD小鼠 纹状体 NOS活性 帕金森病 神经毒性 

分 类 号：R363[医药卫生—病理学]