淫羊藿苷抑制小胶质细胞激活及调控NADPH oxidase通路在抗帕金森病中的作用机制研究

项目名称： 淫羊藿苷抑制小胶质细胞激活及调控NADPH oxidase通路在抗帕金森病中的作用机制研究

项目编号： No.81460556

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张锋

作者单位： 遵义医科大学

项目金额： 50万元

中文摘要： 帕金森病(PD)病因未明且临床缺乏有效治疗药物。小胶质细胞激活介导的神经炎症特别是小胶质细胞内NADPH oxidase(PHOX)调控的活性氧(ROS)释放被认为是多巴胺(DA)神经元死亡主要原因之一。因此，抑制小胶质细胞介导的神经炎症很可能成为治疗PD新策略。淫羊藿苷(ICA)是淫羊藿主要活性成分之一，具有抗炎、抗氧化、抗衰老等作用。但ICA防治PD的研究未见报道。课题组预实验发现：ICA保护大鼠中脑黑质注射LPS造成的DA神经元损伤，且抑制LPS 诱导的小胶质细胞激活并减少PHOX调控的ROS 释放，提示对小胶质细胞激活及PHOX的调控可能是ICA 神经保护重要机制之一。因此本项目拟通过MPTP和LPS诱导两种PD动物模型，进一步观察ICA治疗作用；并采用大鼠原代中脑神经元-胶质细胞共培养模型，深入探讨ICA 对小胶质细胞介导神经炎症及PHOX通路的调控机制，为ICA临床应用提供依据

中文关键词： 淫羊藿苷；帕金森病；神经炎症；小胶质细胞；NADPH；oxidase

英文摘要： The mechanisms responsible for Parkinson's disease (PD) are not fully understood and current therapeutic treatments cannot halt PD progression. Microglia-mediated neuroinflammation and NADPH oxidase-generated reactive oxygen species (ROS) are thought to contribute to dopaminergic (DA) neuronal death. Thus, the inhibition of microglia-mediated neuroinflammation is becoming a promising therapeutic potential for PD. Icariin, a main active component of Epimedium, has been known to possess anti-oxidant, anti-inflammation and anti-aging properties. However, the neuroprotective effects of ICA on PD have not been elucidated. Here, based on our preliminary experiments, we found ICA produced neuroprotection against substantial nigral stereotaxic injection of lipopolysaccharide (LPS)-induced DA neurotoxicity. Moreover, ICA inhibited LPS-induced microglial activation and NADPH oxidase-generated ROS production, suggesting that the inhibition of microglial activation and NADPH oxidase-generated ROS production might be involved in ICA-mediated neuroprotection. Therefore, the present study further elucidated the neuroprotective effects of ICA on 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)- and LPS-induced 2 PD animal models. In addition, rat primary neuron-glia cocultures were performed to demonstrate the possible mechanisms underlying the role of ICA on microglia-mediated neuroinflammation. Taken together, this study extends our understanding of anti-inflammatory activities mediated by ICA and suggests that NADPH oxidase signaling pathways are important action sites for the treatment of PD.

英文关键词： Icariin;Parkinson disease;neuroinflammation;microglia;NADPH oxidase