吡咯喹啉醌对鱼藤酮损伤神经细胞的保护作用及机制研究

项目名称： 吡咯喹啉醌对鱼藤酮损伤神经细胞的保护作用及机制研究

项目编号： No.81201017

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 张琦

作者单位： 南通大学

项目金额： 23万元

中文摘要： 吡咯喹啉醌（PQQ）作为一种新型氧化还原酶辅基，由于其在抗氧化损伤方面独特的优势和可以通过血脑屏障的特性，使将其开发成为具有神经保护作用的药物成为可能，但目前对其作用机制方面还没有深入的报道。本课题组已经报道了PQQ在神经元谷氨酸损伤方面具有保护作用，并对其在细胞内的信号转导途径及抗氧化作用的靶点进行了初探，发现其作用靶点可能为线粒体呼吸链复合物I和III，同时发现PQQ对复合物I抑制剂鱼藤酮损伤的SH-SY5Y细胞具有一定保护作用。本课题以此为基础，试图在体外培养的神经细胞鱼藤酮损伤模型中，发现参与其保护作用的信号分子，探讨其保护作用是否与改善线粒体功能、促进ROS清除和神经递质转运等相关，并通过鱼藤酮前脑内侧束注射建立PD模型大鼠，进一步在动物体内分析其作用及相关机制。本课题的研究对于阐明PQQ的作用机制具有重要意义，为将其开发应用于临床提供可靠的基础实验依据。

中文关键词： 吡咯喹啉醌；鱼藤酮；线粒体；活性氧；多巴胺

英文摘要： Pyrroloquinoline quinone (PQQ) was initially identified as a redox enzyme cofactor, and later proven to be an essential nutrient for animal growth. PQQ not only serves to mediate redox reactions in the mitochondrial respiratory chain, but also plays a potential role of scavenging reactive oxygen species (ROS) and attenuating oxidative stress in mitochondria. Accumulating evidence shows that PQQ can antagonize the oxidative stress-induced cell damage, including reoxygenation injury of heart, ethanol-induced liver damage, and hyperoxia-caused cognitive deficit. Because of the strong ability of scavenging ROS and the property of easily getting through blood-brain-barriers, PQQ has the potential of being developed into a clinical drug with protective functions in nervous system. However, there is rare research about the mechanisms of PQQ, especially in nervous system. Our team has reported that PQQ can protect cultured hippocampal neurons against glutamate-induced cell damage. The inhibition of Ca2+ influx, Caspase-3 activity, and ROS production might be involved in the protective effect of PQQ. The phosphorylation of Akt and JNK signaling pathways was regulated by PQQ treatment after glutamate stimulation, and PQQ-activated Akt signaling promoted the cell survival through modulation of glutamate-induced imbalance b

英文关键词： Pyrroloquinoline quinone (PQQ)；rotenone；mitochondria；reactive oxygen species (ROS)；dopamine