原花青素对氧化应激的营养干预作用及分子机制

Extremely low frequency electromagnetic fields (ELF-EMF) is one of the electromagnetic fields closely related to our life and work, it is a kind of non-thermal effects-based non-ionizing radiation generated from an electromagnetic field within the spectrum of 0-300Hz. The biological effect of ELF-EMF possesses the property of hysteresis, accumulation and amplification, which can lead to biological macromolecules and even body injury. The hazard to health presented by ELF-EMF has caused wide concern. Nutrition advocates adding active substances in the diet to prevent disease in order to improve national health. Procyanidins has been recognized worldwide as food and nutrition factors. In view of the way for the impairment of learning and memory, and brain oxidative stress induced by ELF-EMF, and the intervention effect of procyanidins remain to be answered, the project will investigate the effect of procyadins from lotus seed pods (LSPCs) in the hippocampal neurons and the rats whose learning, memory and brain have been injured by ELF-EMF, and then on this basis, especially attempt to reveal the regulatory role and molecular mechanism of LSPCs on the signaling pathway of the impairment of learning and memory, and brain oxidative stress induced by ELF-EMF, and provide a theoretical basis and scientific support for its in-depth study of the food and health products.

极低频电磁场(ELF-EMF)是频谱在0-300Hz的电磁波发出的以非热效应为主的非电离辐射，是与我们生活和工作最密切的电磁场之一。ELF-EMF虽剂量小，但生物效应有滞后、累积和放大等特性，也会导致生物大分子乃至机体损伤。ELF-EMF的健康危害已引起公众的广泛关注。营养学提倡在饮食中添加活性物质来预防疾病以提高国民健康。因原花青素是世界公认的食品营养因子。故本研究针对ELF-EMF致脑氧化应激损伤学习记忆的途径及原花青素的干预作用不清楚，作用机制缺乏研究的现状，拟以ELF-EMF致小鼠脑氧化应激损伤学习记忆为动物模型，海马神经元为细胞模型，研究莲房原花青素(LSPCs)对ELF-EMF致脑氧化应激损伤学习记忆的预防作用。在此基础上，重点研究LSPCs对ELF-EMF致脑氧化应激损伤学习记忆损伤的信号通路的调控作用及分子机制，最终为其在食品和保健品的深入研究提供理论依据和科学支撑。

本项目针对极低频电磁场（Extremely low frequency electromagnetic fields，ELF-EMF)致脑氧化应激损伤学习记忆的途径及原花青素的干预作用不清楚，作用机制缺乏研究的现状，以ELF-EMF致脑氧化应激损伤学习记忆的小鼠为动物模型，海马神经元为细胞模型，建立了ELF-EMF致脑氧化应激损伤学习记忆的场强效应和时间效应关系；通过动物水平、细胞水平、分子水平以及基因水平研究了莲房原花青素(procyadins from lotus seed pods，LSPCs)对ELF- EMF诱导脑氧化应激损伤学习记忆的预防作用和分子机制；ELF-EMF对神经细胞内micro RNA的影响及LSPCs的调控作用；增加了LSPCs对ELF-EMF致机体衰老和生殖损伤的干预作用研究；LSPCs对ELF-EMF致免疫损伤的干预作用和机制的研究。结果表明，ELF-EMF长期辐照能引起神经元高活性氧自由基(reactive oxygen species, ROS)积蓄，引发脑氧化应激损伤，进而影响学习记忆功能；LSPCs对ELF-EMF致海马神经元和皮层胶质细胞氧化应激均具有预防作用，主要通过激活内生抗氧化酶活力，Ca2+依赖的信号途径、双信使信号途径和线粒体介导的途径减少神经细胞凋亡；LSPCs预防脑氧化应激损伤学习记忆的机制与其有效预防海马神经元突触前兴奋性递质谷氨酸的释放、预防突触可塑性相关蛋白SYN、Arc和MAP-2的表达异常有关；ELF-EMF长期辐照影响神经元microRNA的表达，LSPCs主要通过神经营养因子信号通路、Wnt信号通路、MAPK信号通路对microRNA的表达进行调控；尤其与学习记忆有关的ASK-1/JNK/AP-1信号通路是LSPCs调控ELF-EMF致脑氧化应激损伤学习记忆的主要信号通路之一，ASK-1、JNK和AP-1是该通路的主要效应分子。此外，LSPCs对ELF-EMF致免疫和生殖损伤损伤的均具预防作用。通过本项目的研究明确了长时间ELF-EMF辐照能引起机体氧化应激并引发多系统损伤；同时为LSPCs用于预防ELF-EMF辐射的食品和保健产品的深入研究提供理论依据和科学支撑。