甲基 - 苯基四氢吡啶对脑不对称小鼠纹状体内多巴胺和白介素含量的影响
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国家自然科学基金资助项目(30271211,30371315)、汕头大学研究与发展基金资助项目(L00011).


Effect of MPTP on Striatal Dopamine and Cytokine Levels in Mice With Brain Asymmetry
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This work was supported by grants from The National Natural Sciences Foundation of China (30271211, 30371315), Scientific Research and Development Foundation of Shantou University (L00011).

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    摘要:

    为探讨甲基 - 苯基四氢吡啶 (MPTP) 注射后脑不对称小鼠纹状体内多巴胺降低程度,及纹状体内细胞因子水平变化, C57BL/6J 小鼠经过伸爪取食试验,筛选为反映脑不对称的左利鼠和右利鼠,并接受 25 mg/kg MPTP 腹腔注射连续 5 天,检测注射后的第 1 天,第 3 天和第 14 天纹状体内多巴胺及代谢物含量和细胞因子 IL-1 β、 IL-6 的动态水平 . 结果表明,无论在左利鼠还是右利鼠,纹状体内多巴胺含量在 MPTP 注射后每个检测时间点都显著降低,纹状体内 IL-1 β水平在第 1 天显著降低,纹状体内 IL-6 水平在 MPTP 注射后每个检测时间点也显著降低 . 实验结果同时表明,左利鼠和右利鼠 IL-1 β和 IL-6 的基础水平有显著不同 . MPTP 注射后,与右利小鼠相比,左利小鼠有较高的多巴胺翻转降低和较低的细胞因子表达,而且,纹状体内多巴胺水平与纹状体内 IL-6 水平呈正相关 . 这些结果提示, MPTP 诱导多巴胺丢失伴随着黑质纹状体系统内细胞因子水平的改变,而且,脑不对称有可能通过影响纹状体内细胞因子水平而进一步影响 MPTP 诱导的多巴胺降低的程度 .

    Abstract:

    MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) can induce dopaminergic cell death in substantia nigra of primates and rodents. In order to investigate the effects of brain lateralization on dopamine loss and cytokine variations in mice which were treated with MPTP, male C57BL/6J mice were selected by paw preference test to constitute right pawed mice and left pawed mice. Mice were injected with 25 mg/kg MPTP i.p., for five consecutive days, and killed on day 1, day 3 and day 14 after MPTP injection. The control group was treated with saline. Striatal dopamine and DOPAC contents were measured by HPLC and striatal IL-1 β and IL-6 were quantified by ELISA. The Results showed that after MPTP treatment, dopamine contents decreased at day 1 (74.48%, P<0.001), day 3 (72.84%, P<0.001) and day 14 (63.87%, P<0.01); IL-6 levels decreased on day 1 (P<0.01), day 3 (P<0.01) and day 14 (P<0.01); while IL-1? 茁 levels only decreased on day 1 (P<0.05). Interestingly, behavioral lateralization had effect on dopamine turnover and cytokine variations. In basal condition, the significant difference was found between right pawed mice and left pawed mice in IL-6 level (P<0.05) and IL-1 β level (P<0.001). After MPTP treatment, left pawed mice showed a greater decrease of dopamine turnover (P<0.05) as compared with right pawed mice, at day 3 after treatment, left pawed animals showed a lower levels of IL-6 (P<0.05) and IL-1 β level (P<0.001) as compared with right pawed animals. Furthermore, the positive correlation between striatal IL-6 levels and striatal dopamine contents was found (P<0.001). These results indicated that MPTP-induced dopamine turnover was influenced by behavioral lateralization, possibly through an effect on brain cytokine levels.

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申延琴,李康生,E. MOZE, P. J. NEVEU.甲基 - 苯基四氢吡啶对脑不对称小鼠纹状体内多巴胺和白介素含量的影响[J].生物化学与生物物理进展,2005,32(1):53-59

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