基于Keap1/ARE-Nrf2/ Sirt1通路AHQDS对百草枯特效解毒疗效分析及机制研究

百草枯(Paraquat,PQ)是一种快速除草剂，对提高作物产量起着重要作用。中毒患者死亡率80%，尽管2014年7月1日国家宣布停止PQ水剂的生产，急诊科收治急性 PQ 毒患者数量仍有上升。近期齐鲁医院中毒病房收治了一些膏状或固体颗粒百草枯中毒的病例。目前尚无特异性解毒剂。本课题组前期研究发现：环境中AHQDS与PQ接触后，体系中PQ的浓度逐渐降低，直至PQ全部反应。SD大鼠致死量4倍的PQ，4个小时后灌胃AHQDS，治疗组SD大鼠存活时间大于60天。本课题组用液相色谱-质谱联法、酶偶联法、膜电位法、WB、PCR、免疫荧光、ELISA流式及siRNA干扰技术等方法观察肺组织、细胞内ROS/ MDA /SOD/NADPH/Keap1/ARE-Nrf2/Sirt1表达，旨在评价AHQDS对PQ特效解毒疗效分析及机制研究，为临床百草枯治疗提供新特效解毒剂。

Paraquat (PQ) is a fast herbicide that plays an important role in increasing crop yields. The mortality rate of poisoned patients is 80%. Although the state announced the suspension of production of PQ water on July 1, 2014, the number of patients with acute PQ poisoning in the emergency department still increased. After July 1, 2016, Cases of paste or solid particle paraquat poisoning were treated in the poisoning wards of Qilu Hospital. There is currently no specific antidote. Our previous research found that after exposure of AHQDS to PQ in the environment, the concentration of PQ in the system gradually decreased until PQ reacted. The lethal dose of SD rats was 4 times of PQ, and AHQDS was administered 4 hours later. The survival time of SD rats in the treatment group was more than 60 days. Our group used liquid chromatography-mass spectrometry, enzyme coupling, membrane potential method, WB, PCR, immunofluorescence, ELISA flow and siRNA interference techniques to observe the vector and intracellular ROS/ MDA /SOD/NADPH/ Keap1/ARE-Nrf2/Sirt1/NF-KB/PEAK expression,this aim is to evaluate the efficacy and analysis of AHQDS for PQ specific detoxification, and to provide a new special antidote for clinical treatment of paraquat.