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。

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.