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目的:观察米诺环素(Minocycline,Mino)对Lactacystin(Lac)模型黑质内胶质细胞反应和多巴胺神经元的干预作用。方法:成年SD大鼠30只随机分为对照、Lac1 W、Lac3 W、Lac5 W、Lac+Mino5 W组,进行Lac动物模型制备和Mino给药处理,通过免疫组织化学和Western blot方法,观察iba1(小胶质细胞标志物)、GFAP(星形胶质细胞标志物)、TH(多巴胺能神经元标志物)的表达水平或阳性细胞数量变化,分析评价黑质内胶质细胞反应和多巴胺神经元生存状态。结果:Lac处理模型黑质内胶质细胞呈现动态活化反应。与生理盐水对照组相比,Lac处理均诱导iba1和GFAP表达水平升高,iba1在Lac3 W组显著升高、并持续高水平至Lac5 W(P<0.05)。GFAP表达在Lac1 W已显著升高、维持至Lac3 W和Lac5 W(P<0.05)。伴随胶质细胞的显著活化反应,黑质内TH阳性神经元数量急剧减少(P<0.01)。与Lac5 W组相比,Lac+Mino5 W组呈现对iba1和GFAP阳性胶质细胞的抑制效应、并提高黑质内TH阳性细胞数量,具有统计学意义(P<0.05)。结论:小胶质细胞抑制剂米诺环素给药处理可能通过干扰胶质细胞的异常活化反应、发挥对Lac损伤模型黒质多巴胺能神经元的一定保护作用。
Objective: To observe the effect of minocycline (Mino) on glial cell response and dopamine neurons in substantia nigra of Lactacystin (Lac) model. Methods: Thirty adult SD rats were randomly divided into control, Lac1 W, Lac3 W, Lac5 W and Lac + Mino5 W groups. Animal model of Lac was established and Mino administration was performed. Immunohistochemistry and Western blotting were used to observe the expression of iba1 (Microglial marker), GFAP (astroglial marker), TH (dopaminergic neuron marker) expression levels or changes in the number of positive cells, analysis and evaluation of intranigral gliacyte response and dopamine nerve Yuan living conditions. Results: The glial cells in substantia nigra of Lac treatment showed dynamic activation. Compared with the saline control group, Lac treatment induced iba1 and GFAP expression levels increased, iba1 in Lac3W group was significantly increased, and continued high levels to Lac5W (P <0.05). GFAP expression was significantly elevated in Lac1 W, maintained to Lac3 W and Lac5 W (P <0.05). With the significant activation of glial cells, the number of TH positive neurons in the substantia nigra decreased dramatically (P <0.01). Compared with Lac5 W group, Lac + Mino5 W group showed inhibitory effects on iba1 and GFAP-positive glial cells and increased the number of TH positive substantia nigra cells in substantia nigra (P <0.05). CONCLUSION: Minocycline administration, a microglial inhibitor, may exert a protective effect on the dopaminergic neurons of Lac dopamine model by interfering with abnormal activation of glial cells.