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目的探讨尼古丁对帕金森病(PD)大鼠黑质多巴胺能神经元变性的影响及其机制。方法45只大鼠随机分为PBS对照组(CON)、生理盐水+脂多糖(NS)组、尼古丁+脂多糖(NIC)组,每组15只。黑质内立体定向注射脂多糖(LPS)或PBS后24h,免疫印迹法检测黑质诱导性一氧化氮合酶(iNOS)蛋白表达变化;黑质注射药物后14d,采用免疫组织化学法观察大鼠黑质酪氨酸羟化酶(TH)阳性神经元数量及OX-42阳性细胞形态学变化,RT-PCR及免疫印迹检测黑质TH mRNA及TH蛋白的表达水平。结果与CON组相比,NS组大鼠黑质iNOS表达明显增多,TH阳性神经元、TH mRNA及TH蛋白明显减少,小胶质细胞大多呈胞体大突起短粗的形态;NIC组黑质iNOS表达明显少于NS组,黑质TH阳性神经元、TH mRNA及TH蛋白表达较NS组明显增多,大部分小胶质细胞呈胞体小,突起细长的形态。结论尼古丁可以减轻LPS介导的多巴胺能神经元变性,对多巴胺能神经元有保护作用,其保护机制与抑制小胶质细胞激活、减少iNOS的表达有关。
Objective To investigate the effect of nicotine on the degeneration of substantia nigra dopaminergic neurons in Parkinson’s disease (PD) rats and its mechanism. Methods 45 rats were randomly divided into PBS control group (CON), saline + lipopolysaccharide (NS) group and nicotine + lipopolysaccharide (NIC) group, 15 rats in each group. Immunohistochemistry was used to detect the expression of iNOS protein in substantia nigra after stereotactic injection of lipopolysaccharide (LPS) or PBS for 24 hours. Immunohistochemistry was used to observe the changes of iNOS protein expression The number of tyrosine hydroxylase (TH) -positive neurons and the morphological changes of OX-42 positive cells were detected by RT-PCR and Western blotting. Results Compared with CON group, the expression of iNOS in substantia nigra in NS group was significantly increased, TH-positive neurons, TH mRNA and TH protein were significantly decreased, while microglial cells were mostly short and thick. Compared with NS group, the expression of TH positive neurons, TH mRNA and TH protein in substantia nigra significantly increased compared with those in NS group. Most microglial cells were small and protuberant. Conclusion Nicotine can reduce the degeneration of dopaminergic neurons induced by LPS and protect the dopaminergic neurons. The protective mechanism is related to the inhibition of microglial activation and the decrease of iNOS expression.