美满霉素对帕金森病大鼠黑质多巴胺能神经元损伤的保护作用

The neuroprotective effects of Minocycline on degenerative dopaminergic neurons in Parkinson's disease rat model

目的观察美满霉素(MC)对脂多糖(LPS)所致帕金森病(PD)大鼠黑质多巴胺能(DA)神经元损伤的保护作用。方法黑质内注射LPS制作PD大鼠模型。应用MC对实验动物进行处理。采用行为学、酪氨酸羟化酶(TH)、核因子-κB(NF-κB)等免疫组化及免疫印迹技术观察MC的神经保护作用。结果对照组大鼠无行为变化,PD组大鼠平均旋转圈数为196.90±9.52,MC组为120.03±10.50,差异非常显著(p<0.01)。免疫组化表明对照组TH阳性神经元数量较多,PD组神经元数量明显减少或消失(p<0.01),MC组TH阳性神经元数与PD组相比明显增加(p<0.01);对照组黑质仅见少数NF-κB阳性细胞,无明显核转位现象,PD组黑质NF-κB阳性细胞较多,部分细胞有明显核转位现象,与PD组相比,MC组NF-κB阳性细胞数明显减少(p<0.01);对照组黑质OX-42小胶质细胞呈分枝状,胞体较小突触细长,PD组黑质小胶质细胞大部分呈圆形,突起少而短甚至消失,与PD组相比,MC组呈激活状态的小胶质细胞数量明显减少。Western blotting分析结果相同。结论 MC可防护LPS所致黑质DA能神经元损伤,具有神经保护作用。

Objective To observe the neuroprotective effect of Minocycline （MC） on degenerative dopaminergic neurons by lipopolysaccharide（LPS） in SD rats. Methods SD rats were randomly divided into control group, LPS group （SD rat models made by intranigral injection of LPS） and MC group（administered by oral garage before LPS administration）. Behaviour study, tyrosine hydroxylase（TH） and Nuclear factor-κ B（NF-κ B） immunohistochmistry and Western blotting were performed . Results The PD group presented with significantly increased mean number of rotation behavior compared with MC group （P 〈0.01）, but with no apomorphine-induced rotation behavior in control group. The levels of TH positive product in substantial nigra was significantly decreased （P〈0.01） in PD group than in control group, but higher than in MC group. The levels of NF-κ B positive product were upregulated in PD group than in control, but lower than in MC group.The percentage of OX-42 positive microglias was increased in PD group than in contol but decreased than in MCgroup. Conclusion MC may have neuroprotective effects on the degenerative dopaminergic neurons caused by LPS in vivo.