NADPH抑制MPTP诱导的帕金森病中的氧化应激和胶质细胞的激活
首发时间:2018-03-06
摘要:目的:研究在MPTP 诱导的帕金森症模型中NADPH对神经炎症的调节作用及其机制。方法:以C57BL/6 小鼠为研究对象,设置空白对照组、模型组和 5 mg/kg、10 mg/kg 两个剂量的NADPH的治疗组。分别通过行为学评估小鼠运动功能;Western blot 检测酪氨酸羟化酶(THase)和炎症相关通路蛋白(COX2,p38MAPK)的表达情况;免疫组织化学染色及Western blot检测GFAP、Iba-1的表达情况;用DHE探针标记检测小鼠中脑腹侧区及小胶质细胞内活性氧 (ROS) 水平的变化;应用ELISA方法测定中脑腹侧区炎症因子IL-1β和TNF-α的表达水平。结果:相比较模型组,NADPH治疗组小鼠行为学障碍及THase减少情况明显改善,并可以抑制ROS生成,胶质细胞的激活,炎症蛋白的产生及p38MAPK 通路的激活。结论:NADPH可以通过抑制神经炎症来减轻MPTP诱导的小鼠运动功能障碍和黑质多巴胺神经元损伤,可能与其抑制ROS的过量产生有关。
关键词: 药理学 NADPH 活性氧 p38MAPK 炎症 帕金森症
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NADPH inhibits oxidative stress and the activation of glial cells in MPTP-induced Parkinson\'disease
Abstract:Objective: To investigate whether NADPH could attenuate neuroinflammation in MPTP-induced rodent model of Parkinson\'s disease. Methods: 80 adult male C57BL/6 mice were randomly divided into the following four groups, comprised of 20 animals in each group: (1) Control group; (2) MPTP group; (3) NADPH (5 mg/kg) + MPTP group and (4) NADPH(10 mg/kg) + MPTP. Behavioral tests were carried out to assess the motor function. Western blot analysis was performed to examine the protein levels of tyrosine hydroxylase (THase), and several signaling proteins associated with neuroinflammation (COX2, p38MAPK). Immunohistochemical staining and Western blot analysis were used to assess the protein levels of GFAP and Iba-1 in SNpc. Intracellular ROS levels in the SNpc of mice and BV2 cells were analyzed with DHE staining. ELISA was applied to measure the inflammatory cytokines of IL-1β and TNF-α in the ventral midbrain of mice. Results: Compared to MPTP group, the behavioral disorders and loss of dopaminergic neurons in the NADPH treated group were significantly improved, and inhibited the production of ROS, the activation of glial cells, the production of inflammatory protein and the activation of p38 MAPK pathway. Conclusion:NADPH can reduce motor dysfunction and the loss of dopaminergic neurons induced by MPTP in substantia nigra by inhibiting neuroinflammation, which may be related to its inhibition of excessive production of ROS.
Keywords: Pharmacology NADPH ROS p38MAPK inflammation Parkinson\'s disease
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NADPH抑制MPTP诱导的帕金森病中的氧化应激和胶质细胞的激活
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