NMDA受体是兴奋性毒性损伤的关键分子，但其拮抗剂在临床试验中显示明显的副作用，因而寻找新的NMDA受体靶向药物异常重要。染料木素磺酸钠(GSS)是对染料木素进行结构修饰的强水溶性物质。前期结果表明，与染料木素相比，GSS脑保护作用明显提高，有效保护剂量显著降低，其机制可能与ERK1/2信号通路激活、GluN2B蛋白水平下调有关。结合染料木素能激活雌激素膜受体GPR30的特性，我们推测GSS很可能通过GPR30调控与细胞损伤信号密切相关的突触外GluN2B型NMDA受体功能而发挥对脑缺血再灌注损伤的保护作用。本项目拟通过分子生物学、电生理学、形态学和药理学等方法，分别从离体和在体水平明确GSS在脑缺血再灌注损伤中保护作用，并对GSS是否通过激活GPR30进而调控GluN2B型NMDA受体功能进行深入研究。该项目有助于深入了解GSS的脑保护作用及机制，为缺血性脑病的预防和治疗提供新线索。

NMDA (N-methyl-d-aspartate) receptors are key molecules involved in excitotoxicity following cerebral ischemia/reperfusion injury. However, NMDA recptor antagonists show prominent side effects in clinical trials. Finding new drugs targeting NMDA receptors is of great significance. Genistein sodium sulfonate(GSS) is novel water soluble substances modified from genistein. Our preliminary data indicate that the neuroprotective effects of GSS against cerebral ischemia is significantly improved compared with genistein and the effective dose was greatly decreased. Thus GSS is a promising drug for cerebral ischemia. Activtion of ERK1/2 signaling pathway and decreased protein level of GluN2B subunit of NMDA receptors might contribute to the neuroprotective effets of GSS. As genistein can activate the membrance estrogen receptor,we speculate that GSS might also have the abitity to activate membrance estrogen receptor and regulate the level and activation of extrasynaptic GluN2B-containing NMDA receptors, which are closely related with cell injury, thus protect against cerebral ischemia/reperfusion injury. In the present project, we will further investigate the neuroprotective effects of GSS through in vitro and in vivo studies and educidate whether GSS can regulate the protein level and activation of GluN2B-containing NMDA receptors throuth activating GPR30,using molecular biological, electrophysiological, morphological, pharmacological and behavioral methods. The present project will be helpful for our understanding of the neuroprotective role of GSS and its underlying mechanisms and will provide a new clue for the clinical preventive medication and treatment of ischemic cerebrovascular disease.