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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 protective effect of minocycline (MC) on dopaminergic neuron damage in the substantia nigra of Parkinson’s disease (PD) rats induced by lipopolysaccharide (LPS). Methods PD rats were made by injection of LPS into substantia nigra. Experimental animals were treated with MC. The neuroprotective effects of MC were observed by immunohistochemistry and immunoblotting using behavior, tyrosine hydroxylase (TH) and nuclear factor-κB (NF-κB). Results There was no behavioral change in the control group. The mean number of rotations in the PD group was 196.90 ± 9.52 and in the MC group was 120.03 ± 10.50, the difference was significant (p <0.01). Immunohistochemistry showed that the number of TH-positive neurons in the control group was larger than that in the PD group (p <0.01), and the number of neurons in the PD group was significantly decreased or disappeared (p <0.01) There were only a few NF-κB positive cells in group substantia nigra with no significant nuclear translocation. There were more NF-κB positive cells in substantia nigra in substantia nigra and some nuclear translocation in PD group. Compared with PD group, NF-κB OX-42 microglial cells in the substantia nigra were dendritic and had small synaptic slender body cells in the control group. Most of the substantia nigra microglial cells in the PD group were round, Less and even disappeared. Compared with PD group, the number of activated microglia in MC group decreased significantly. Western blotting analysis of the same results. Conclusion MC can protect DA neurons of substantia nigra induced by LPS and has neuroprotective effect.