上海交通大学学报（医学版）

›› 2012, Vol. 32 ›› Issue (6): 711-.doi: 10.3969/j.issn.1674-8115.2012.06.005

• 论著（基础研究） • 上一篇    下一篇

米诺环素抑制促炎因子生成保护多巴胺能神经元

汪锡金1, 颜志强2, 谷胜利3, 叶 民4, 刘振国1   

  1. 1.上海交通大学 医学院附属新华医院神经内科, 上海200092； 2.中国科学院上海生命科学研究院实验动物中心, 上海 201615； 3.上海长宁区同仁医院神经内科, 上海 200050； 4.南京明基医院神经内科, 南京 210019
  • 出版日期:2012-06-28 发布日期:2012-07-02
  • 通讯作者: 刘振国, 电子信箱: zhenguoliu2004@yahoo.com.cn。
  • 作者简介:汪锡金（1971—）, 男, 主治医师, 博士；电子信箱: wangxijingcn@yahoo.com.cn。
  • 基金资助:

    国家自然科学基金（81171204, 81171203, 30772280）

Minocycline protects dopaminergic neurons by inhibiting production of proinflammatory factors

WANG Xi-jin1, YAN Zhi-qiang2, GU Sheng-li3, YE Min4, LIU Zhen-guo1   

  1. 1.Department of Neurology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China；2.Shanghai Laboratory Animal Center, Chinese Academy of Sciences, Shanghai 201615, China；3.Shanghai Tongren Hospital, Shanghai 200050, China；4.Department of Neurology, Nanjing BenQ Hospital, Nanjing 210019, China
  • Online:2012-06-28 Published:2012-07-02
  • Supported by:

    National Natural Science Foundation of China, 81171204, 81171203, 30772280

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摘要：

目的 探讨米诺环素对炎症介导的中脑多巴胺能神经元损伤的影响。方法 应用脂多糖处理中脑原代神经元/胶质细胞培养体系建立SD大鼠多巴胺能神经元损伤的炎症机制模型，于脂多糖处理该培养体系前或后加入米诺环素，免疫细胞化学法检测酪氨酸羟化酶阳性神经元的数目，液闪测定法测定多巴胺摄取力，并检测肿瘤坏死因子-α（TNF-α）(ELISA法)、白介素-1β（IL-1β）(ELISA法)、一氧化氮（NO）(Griess法）和超氧阴离子（细胞色素C还原法）等促炎因子的变化。结果 米诺环素（2～10 μmol/L）前处理对脂多糖（1～100 ng/mL）诱导的中脑多巴胺能神经元损伤具有显著的保护作用，呈剂量依赖性；米诺环素（10 μmol/L）后处理对脂多糖（10 ng/mL）诱导的中脑多巴胺能神经元损伤也具有显著的保护作用；米诺环素显著降低促炎因子TNF-α、IL-1β、NO和超氧阴离子的生成。结论 米诺环素在脂多糖处理的中脑神经元/胶质细胞培养体系中可能通过抑制促炎因子生成保护多巴胺能神经元。

关键词: 帕金森病, 米诺环素, 多巴胺能神经元, 促炎因子

Abstract:

Objective To investigate the effect of minocycline on inflammation-induced dopaminergic neurodegeneration. Methods SD rat model of inflammation-induced dopaminergic neurodegeneration was established in mesencephalic neuron/glia cultures by lipopolysaccharides. The culture system was treated by minocycline before or after the addition of lipopolysaccharides. The number of dopaminergic neurons was determined by immunocytochemistry and cell counting. Cell bioactivity was detected by liquid scintillation uptake assay. Besides, the changes of key proinflammatory factors such as tumor necrosis factor-α (TNF-α)(by ELISA), interleukin-1β (IL-1β)(by ELISA), nitric oxide (NO)(by Griess method) and superoxide (by cytochrome C reduction method) were examined in the cultures. Results Minocycline (2-10 μmol/L) pretreatment dose-dependently attenuated the reduction in dopamine uptake and dopaminergic cell number in mesencephalic cultures treated with lipopolysaccharides (1-100 ng/mL). Minocycline (10 μmol/L) posttreatment also protected dopaminergic neurons from lipopolysaccharides (10 ng/mL)-induced neurodegeneration in neuron/glia cultures. Minocycline pretreatment and posttreatment significantly inhibited the production of TNF-α, IL-1β, NO and superoxide in neuron/glia cultures. Conclusion Minocycline may protect mesencephalic dopaminergie neurons treated with lipopolysaccharides by inhibiting the production of proinflammatory factors.

Key words: Parkinson´s disease, minocycline, dopaminergic neurons, proinflammatory factors