临床常用大剂量甘草解急性药物中毒，对缓解中枢中毒效果显著，其作用机制尚未完全阐明。课题组已结题基金项目研究发现，甘草具有上调转运体的功能和表达促进外排，胃肠道直接相互作用，以及通过Nrf2/ARE通路调控等多重解毒机制。结合文献对Nrf2通路下游损伤相关因子HMGB1多个结合位点及乙酰化的最新进展，本项目进一步提出“甘草通过维持脑内生化环境稳态而发挥中枢解毒作用，其中HMGB1是发挥解毒作用的关键因子”的假说。选择典型中枢毒性中药马钱子为模型毒物，SD大鼠为实验动物，微透析采样、UPLC-MS/MS和库伦电化学在线分析，以及分子生物学检测技术，从神经递质平衡角度，通过甘草对脑内相关酶、神经递质和受体的影响，构建脑内完整生化环境变化谱图，并通过HMGB1-TLR-4/RAGE通路探究甘草的神经保护机制，以验证该假说。对阐明甘草解毒的中枢效应过程和生化基础，揭示甘草解毒的潜在机理提供科学依据。

High dose licorice is always used to relieve acute drug poisoning and has a significant effect in relieving central nervous system toxicity, but the specific mechanism has not yet been fully elucidated. The previous study about licorice detoxification mechanism founded by Natural Science Foundation of China demonstrated that licorice exerts detoxification function from multiple aspects. Licorice can up-regulate the expression and function of efflux transporter and then promote central toxic efflux. At the same time, licorice can directly interact with poisons in the gastrointestinal tract. In addition, the detoxification of licorice can be played through its regulating effect of Nrf2/ARE signaling pathway. Based on the recent advances in literatures on multiple binding sites and acetylation of HMGB1,a downstream damage-related factor of Nrf2 pathway,in this project, the hypothesis “licorice relieves central nervous system toxicity rapidly by maintaining brain biochemical environmental stability, and HMGB1 may be the key factor in detoxification process” is been proposed. To explore the influence of licorice on biochemical environment spectrum, Semen Strychni which has central nervous system toxicity is chosen as model poison, SD rats are experimental animal, using microdialysis, UPLC-MS/MS, electrochemical online detection and molecular biology technology to detect the change trend of neurotransmitters, key metabolic enzymes and neurotransmitter receptors in the brain. Then further study the neuroprotective mechanism of licorice through HMGB1-LTR-4/RAGE signaling pathway. This research provides scientific basis to clarify the central effect and biochemical basis of licorice detoxification process, and reveal the potential detoxification mechanism of licorice.