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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。
To investigate the changes of nitric oxide synthase (NOS) activity in brain tissue of Parkinson disease (PD) model mice and to explore the possible mechanism of nicotine in PD. In this experiment, PD model of C5 7BL mice was established by using 1-methyl-4-phenyl 1,2,6,6-tetrahydropyridine (MPTP). Colorimetric analysis, HPLC and immunohistochemistry were used to detect MPTP and nicotine NOS activity, dopamine (DA), DOPAC, HVA and tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS) immunohistochemistry. The results showed that nicotine significantly inhibited MPTP-induced increase in NOS activity (15.61 IU ± 1.5 IU and 13.0 9 IU ± 0.89 IU, P <0.01, respectively) and the number of nNOS-positive neurons 6 8.6 1 ± 3.84 and 39.2 6 ± 2 .6 4, P <0.01), and could significantly reduce the MPTP-induced striatum DA in mice (0.73 μg ± 0.2 8μg and 1.4 0 μg ± 0.19μg, P <0.01), DOPAC (0.41 μg / ml and 0.90 μg / 0. 9 μg / g brain tissue respectively, P <0. 0 1), HVA (0.31 μg ± 0.07 μg and 0.47 μg ± 0.19 μg, respectively, P <0.01), and impairment of TH positive nerve fibers. Therefore, nicotine may have a protective effect on the neurotoxicity of MPTP by inhibiting the activity of nNOS.