目前，除虫菊酯类农药使用占整个杀虫剂面积的1/4，研究Ⅱ型除虫菊酯类农药氯氰菊酯对中枢神经系统神经元的影响，对于应对日益严重的农药残留问题至关重要。我们研究显示，来自植物中的原花青素能够阻断氯氰菊酯暴露造成的氧化应激损伤及Nrf2核转位，同时使表达增强的下游靶激酶向基础水平回调。在Nrf2/ARE通路参与氯氰菊酯和原花青素对细胞的损伤与保护作用中，我们想知道上游信号途径PI3K/Akt通路是否参与调控。该项目采用RNAi技术，构建针对C57BL/6J小鼠Nrf2基因的慢病毒载体，使小鼠皮层神经元Nrf2基因表达沉默，阻断Nrf2及其下游靶激酶表达。从行为学观察、中枢神经系统单胺类神经递质含量测定到细胞活性、形态、氧化应激指标、凋亡检测及基因、蛋白水平方面进行研究，探讨原花青素对P13K/Akt/Nrf2信号通路在氯氰菊酯所致神经元毒性效应中的调控。这为有效处理农药残留提供实验和理论依据。

Currently, the using area of pyrethrins all over the world is about 1/4 of the whole pesticide using region. Therefore, it is of great importance to study the influence of type II pyrethrins cypermethrin on central nervous system neurons for coping with the increasingly serious problem of pesticide residue. Our study shows that natural-occurring substance from plants-procyanidine, can block oxidative stress injury and Nrf2 nuclear translocation caused by cypermethrin exposure; meanwhile, it can make downstream target kinase with enhanced expression back to the basic level. During the adjustment process of Nrf2/ARE signal pathway involving cellular damage and protective effect medicated by cypermethrin and procyanidine, it is important to know whether the upstream signal path PI3K/Akt signal pathway involves in the regulation. RNAi technique was adopted in this project to establish lentiviral vectors targeted on C57BL/6J mice Nrf2 gene, silence cerebral cortex neuron Nrf2 gene expression of mice, block Nrf2 and its downstream target kinase expression and block the activation of P13K. In this project, behavior observation of living animals,central nervous system monoamine neurotransmitter content, cell activity, form, oxidative stress of neurons, cell apoptosis were detected and gene, protein level were studied to discuss the regulation of P13K/Akt/Nrf2 signal pathway by procyanidine in the neuronal toxicity effect caused by cypermethrin. This has provided experimental and theory evidenced for dealing with the problem of pesticide residue effectively.