褐藻硫酸化甘露葡萄糖醛酸寡糖的构效关系与抗帕金森病机制研究

项目名称： 褐藻硫酸化甘露葡萄糖醛酸寡糖的构效关系与抗帕金森病机制研究

项目编号： No.41506165

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 天文学、地球科学

项目作者： 金维华

作者单位： 浙江工业大学

项目金额： 21万元

中文摘要： 帕金森病（Parkinson’s disease，PD）是一种多发于中老年人、以运动障碍为主要表现的神经系统退行性疾病。抑制多巴胺（DA）神经元凋亡，从而保护神经系统，已成为PD治疗的研究热点。课题申请人发现昆布来源的甘露葡萄糖醛酸寡糖及其硫酸化衍生物对DA神经元有显著的保护作用，其作用机制可能与抗DA神经元凋亡活性有关。本课题一方面拟通过定位硫酸化修饰制备得到不同硫酸化取代位置和不同硫酸化程度的硫酸化甘露葡萄糖醛酸寡糖单体，从而阐述硫酸化方式与硫酸化程度与抗PD活性、抗DA神经元凋亡作用的构效关系；另一方面，拟通过PD细胞模型和PD小/大鼠模型，检测与神经元凋亡相关的基因和蛋白的表达，探讨抗DA细胞凋亡的作用机制。研究结果可为硫酸化甘露葡萄糖醛酸寡糖作为新型抗帕金森病候选药物奠定理论基础。

中文关键词： 甘露葡萄糖醛酸寡糖；硫酸化修饰；构效关系；抗帕金森病；机制

英文摘要： Parkinson’s disease (PD), a neurodegenerative disease, often occurs in the elderly people. And the main show is movement obstacle. One research focus of the PD treatment is to inhibit the apoptosis of dopamine (DA) neuron for the protection of nervous system. Our previous studies showed that glucuromannan oligosaccharides and their sulfation derivatives had significant neuropretection on the DA neuron. This might be attributed to the anti-apoptosis of DA neuron. Thus, on the one hand, sulfated glucuromannan oligosaccharides with different patterns and degrees of sulfation were prepared through discriminative protection to explain the relationship between sulfation pattern and degree and anti-PD activity and anti-apoptosis of DA neuron; On the other hand, detecting the neuronal apoptosis associated gene and protein expression both in vitro and in vivo is to discuss the mechanism of anti-apoptosis of DA neuron. The results would establish a theoretical basis for the new candidate sulfated glucuromannan oligosaccharides for the PD treatment.

英文关键词： glucuronomannan oligosaccharides ;sulfation ;structure-activity relationship;anti-Parkinson's disease;mechanism