C60衍生物通过调控Nrf2/NF-κB炎症平衡体系抑制小胶质细胞活化的研究

项目名称： C60衍生物通过调控Nrf2/NF-κB炎症平衡体系抑制小胶质细胞活化的研究

项目编号： No.31271071

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 叶社房

作者单位： 厦门大学

项目金额： 80万元

中文摘要： 脑神经退行性病变是严重危害人类健康的神经系统疾病，目前尚无理想防治药物。小胶质细胞活化介导的炎性神经变性损伤是多种脑神经退行性病变的主要致病机制，因此抑制小胶质细胞活化是防治这类疾病的重要干预策略之一。水溶性富勒烯C60衍生物特殊的理化性能赋予其多重独特的生物学活性，使其在神经退行性病变防治中显示出潜在的应用前景。然而，C60衍生物对小胶质细胞活化行为的影响及机制尚不清楚。本项目通过脂多糖（LPS）活化的小胶质细胞为体外模型，结合小胶质细胞活化介导的脑神经损伤体内模型，从分子、细胞及动物整体多层次、纵深探讨羟基或羧基化C60衍生物对活化小胶质细胞诱导的氧化应激及炎症反应的影响，阐明其对Nrf2/NF-κB炎症平衡体系的调控作用，以期揭示羟基或羧基化C60衍生物抑制活化小胶质细胞介导的神经组织变性的新机制。研究有望为脑神经退变性疾病的防治以及新型神经保护药物的开发提供科学依据。

中文关键词： 富勒烯衍生物；小胶质细胞活化；Nrf2；NF-kappaB；神经系统退行性病变

英文摘要： Mounting evidence indicates that microglial activation contributes to neuronal damage in neurodegenerative disorders. Activated microglia can induce and release neurotoxic proinflammatory factors as well as reactive oxygen species (ROS), which lead to inflammation-mediated neuronal cell death.Therefore, control of microglial activation may alleviate the progression of neurodegeneration,suggesting that development of anti-inflammatory or antioxidant drugs could provide a potential therapeutic approach for neurodegenerative conditions.Research in the field of water-soluble C60 fullerene derivatives has significantly increased due to the broad range of biological activities found for these compounds.As the peculiar structure of C60 fullerenes not only serve as "radical sponge", but also may possess higher physical stability when in contact with biological fluids, show good biocompatibility in vivo and in vitro, and pass through the blood-brain barrier, the exceptional radical-scavenging property and biophysical properties of fullerene make them promising pharmacophore for development of drugs targeting neurodegenerative diseases. Although C60 fullerene derivatives have been reported to possess excellent neural protective efficacy in a broad spectrum of neurodisorders, the effect of C60 fullerene derivatives on micr

英文关键词： Fullerene；microglia；Nrf2；NF-kappaB；neurodegenerative disorders.