依达拉奉对帕金森病模型小鼠多巴胺能神经元的保护作用
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河北省卫生厅课题(20120056),河北省引进留学人员经费资助项目(2011-2013).


Neuroprotective effects of edaravone on dopaminergic neurons in Parkinson’s mice
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Supported by Program of the Health Department of Hebei Province (20120056) and Project for Introduced Scholars who have studied abroad of Hebei Province (2011-2013).

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    摘要:

    目的 探讨依达拉奉(edaravone)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的C57BL/6J帕金森病模型小鼠的保护作用及相关机制。方法 90只雄性C57BL/6J小鼠随机分为依达拉奉组(ED组)、帕金森病模型组(PD组)和生理盐水对照组(NS组),每组30只。ED组和PD组小鼠给予皮下注射MPTP建立PD模型后,ED组给予依达拉奉(3 mg/kg)治疗。用滚轴实验检测小鼠的旋转次数,用免疫组织化学实验检测小鼠黑质酪氨酸羟化酶(TH)的表达, 用RT-PCR和免疫印迹实验分别检测小鼠黑质脑源性神经营养因子(BDNF) mRNA与蛋白的表达。结果 与NS组比较, ED组、PD组小鼠在滚轴实验中的旋转次数下降(P<0.05, P<0.01), 黑质 TH表达减少(P<0.05, P<0.01), 黑质BDNF的mRNA(P均<0.01)和蛋白(P均<0.05)表达降低;与PD组比较,ED组小鼠在滚轴实验中的旋转次数增加(P<0.05),黑质TH表达增加(P<0.05), 黑质BDNF的mRNA(P<0.01)和蛋白(P<0.05)表达升高。结论 依达拉奉可增加C57BL/6J PD模型小鼠黑质区BDNF的mRNA及蛋白表达,降低MPTP对小鼠黑质的损伤,对多巴胺能神经元有保护作用。

    Abstract:

    Objective To explore the neuroprotective effects of edaravone in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-C57BL/6J-Parkinson’s disease (PD) model mice and the related mechanisms. Methods Totally 90 male C57BL/6J mice were evenly randomized into edaravone (ED) group, PD model group and normal saline (NS) group. Subcutaneous injection of MPTP was used to make PD model, and ED group was then administered with ED(3 mg/kg). Rotarod number was detected by rotarod test. Tyrosine hydroxylase-immunoreactive (TH-ir) neurons expression in the substantia nigra (SN) of mice was observed by immunohistochemistry staining. Brain-derived neurotrophic factor(BDNF) mRNA and protein expression in the SN of mice were tested by RT-PCR and Western blotting analysis, respectively. Results Compared with NS group, rotarod numbers in ED and PD groups were significantly less (P<0.05, P<0.01), the number of TH-ir neurons in SN was significantly reduced (P<0.05, P<0.01), and BDNF mRNA (all P<0.01) and protein (all P<0.05) expression was significantly decreased. Compared with PD mice, rotarod number in ED mice was significantly more (P<0.05), the number of TH-ir neurons in the SN was significantly increased (P<0.05), and BDNF mRNA (P<0.01) and protein (P<0.05) expression was significantly enhanced. Conclusion ED can increase the expression of BDNF mRNA and protein in the SN of C57BL/6J-PD model mice, alleviate MPTP damage, and has a protection effect on dopaminergic neurons.

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  • 收稿日期:2013-02-26
  • 最后修改日期:2013-03-18
  • 录用日期:2013-05-15
  • 在线发布日期: 2013-08-20
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