小胶质细胞介导帕金森病小鼠的氧化应激损伤

背景：研究证实,小胶质细胞诱导型一氧化氮合酶可增加多巴胺能神经元对百草枯的摄取,造成百草枯对多巴胺能神经元的特异性杀伤作用。帕金森病的黑质纹状体存在小胶质细胞的激活,但其产生氧化应激作用机制尚不明确。 目的：建立帕金森病小鼠模型,观察小胶质细胞介导的氧化应激损伤在帕金森病中的作用。 方法：36只C57BL/6小鼠随机分为帕金森病模型组和对照组,每组18只。以腹腔注射百草枯10 mg/kg为模型组,等体积生理盐水为对照组,分别观察小鼠行为活动改变。采用高效液相法测定两组小鼠黑质纹状体多巴胺的含量及免疫组织化学方法检测两组小鼠黑质部位酪氨酸羟化酶、mac-1蛋白表达,同时应用化学比色法测定两组小鼠黑质部位超氧化物歧化酶、还原性谷胱甘肽、谷胱甘肽过氧化物酶活性和丙二醛水平的变化。 结果与结论：模型组小鼠自发行为活动较对照组减少(P < 0.05)。高效液相法检测模型组小鼠黑质纹状体多巴胺含量及酪氨酸羟化酶蛋白的表达均显著低于对照组(P < 0.05),mac-1蛋白表达高于对照组(P < 0.05)。模型组超氧化物歧化酶、还原性谷胱甘肽、谷胱甘肽过氧化物酶活性较对照组均显著下降(P < 0.05),丙二醛水平较对照组显著升高(P < 0.05)。提示中脑黑质部位小胶质细胞的激活致使氧化应激反应增强及抗氧化保护作用减弱可能是引起帕金森病发病的重要机制。

Microglia-mediated oxidative stress injury in a mouse model of Parkinson’s disease

BACKGROUND:In microglia, inducible nitric oxide synthase can induce dopaminergic neurons to promote the intake of paraquat. However, exposure to paraquat can result in specific injury to dopaminergic neurons. The substantia nigra pars compacta in patients has activated microglia, but the role of oxidative stress injury is unkonwn. OBJECTIVE:To explore the role of microglia mediated oxidative stress injury in mouse models of Parkinson’s disease. METHODS:Thirty-six C57BL/6 mice were randomly divided into two groups with 18 mice in each: Parkinson’s disease group and control group. The model of Parkinson’s disease was established by intraperitoneal injection of paraquat to mice (10 mg/kg). The control group was given the same dose of normal saline as paraquat. Adult spontaneous motor activity was observed in the two groups. The level of dopamine in the substantia nigra pars compacta was observed by high-performance liquid chromatography. The expressions of tyrosine hydroxylase and mac-1 in the substantia nigra pars compacta were measured by immunohistochemical staining under optical microscope. The spectrophotometry was used to detect the activities of glutathione, superoxide dismutase and glutathione peroxidase and the content of malondialdehyde in the substantia nigra pars compacta. RESULTS AND CONCLUSION:Parkinson’s disease group showed a marked hypoactive behavior and the number of microglia as compared with the control group (P < 0.05). Immunohistochemical staining showed tyrosine hydroxylase expression in the Parkinson’s disease group was decreased, but mac-1 was increased compared with the control group (P < 0.05). The content of dopamine in the substantia nigra pars compacta was lower than that in the control group detected by high-performance liquid chromatography (P < 0.05). The activities of glutathione, superoxide dismutase, and glutathione peroxidase were significantly reduced in the Parkinson’s disease group, but the content of malondialdehyde was increased as compared with the control group (P < 0.05). These findings indicate that activated microglia in the substantia nigra pars compacta can strengthen oxidative stress injury and weaken anti-oxidative protection, which may be an important pathogenesis of Parkinson’s disease.