脑缺血再灌注损伤的病理机制复杂，针对关键靶点对其进行有效防治是国内外研究的热点。有研究表明内质网应激（ERS）参与了缺血再灌注损伤，并与炎性反应、氧化应激关系紧密，提示ERS对p38 MAPK信号通路可能起调控作用。我们研究发现，植物雌激素鹰嘴豆芽素A可抑制p38，减轻炎性反应和抗凋亡，对大鼠脑缺血再灌注具有保护作用。这一作用是否与ERS对p38 MAPK信号通路的调控有关，值得深入探讨。故提出假设：脑缺血再灌注损伤时ERS持续存在，不能恢复神经细胞自稳，激活了p38 MAPK信号通路，导致脑组织炎性反应和细胞凋亡，鹰嘴豆芽素A可能影响ERS，抑制p38 MAPK激活。本课题拟通过在神经细胞和动物脑内过表达或沉默ERS中的关键分子GRP78和CHOP，研究ERS对p38 MAPK信号通路的调控，探讨其在脑缺血再灌注中的作用，及鹰嘴豆芽素A的治疗机制，为缺血性脑卒中的防治开拓新思路。

Various pathophysiologic mechanisms are involved in the cerebral ischemia/reperfusion (I/R) injury. The contemporary focal issues are searching for the promising targets in the prevention and treatment of stroke. It has reported that endoplasmic reticulum stress (ERS) gets involved in the pathological damage process of I/R injury, and there exist close correlations between ERS, inflammation, and oxidative stress. It is suggested that ERS probably modulates p38 MAPK signaling pathway in cerebral I/R injury. We have found that biochanin A, a typical phytoestrogen, exhibited anti-inflammatory and anti-apoptosis effects by inhibiting p38 MAPK signaling pathway, subsequently improving the brain function in cerebral I/R rats. However, it deserves further research whether the neuroprotective effect of biochanin A is related to the modulation of ERS on p38 MAPK signaling pathway in I/R injury. Therefore, we proposed the following assumption: the neurons endoplasmic reticulum stress continuously exists in cerebral I/R, and it can reduce the capacity of neurons restoring from disorders, subsequently p38 MAPK signaling pathway is activated. As a result, the infernal circle finally leads to brain tissue inflammatory reaction and neurons apoptosis. The neuroprotective effect of biochanin A probably related to affecting ERS and inhibiting p38 MAPK signaling pathway. The project aims to, through overexpressing and silencing GRP78 or CHOP (the key molecules in the ERS), explore the relationship between ERS and p38 MAPK signaling pathway, research its effects in cerebral I/R injury and the therapeutical mechanism of biochanin A, which provide theoretical basis and new ideas on the application of biochanin A in the treatment of ischemic stroke.