中医药治疗脑卒中及其后遗症是常用治疗手段，然而其作用机制及靶点不明制约着中医药的发展。经方栝楼桂枝汤临床上用于脑卒中后康复有独特疗效。前期研究表明该方具有显著抗大鼠脑缺血再灌注损伤（MCAO）后肢体痉挛的作用，明显抑制神经元凋亡，显著降低细胞内Ca2+浓度，上调钙信号转导通路中多个关键分子的表达，提示该方可能通过调控细胞内钙稳态和神经递质平衡，从而激活钙信号转导通路、抑制神经元凋亡治疗缺血性卒中后肢体痉挛。本研究拟建立MCAO模型及NMDA诱导神经元兴奋性毒性损伤模型，结合MRI多模态成像技术观察药物抗大鼠MCAO后肢体痉挛及兴奋性毒性作用，并从钙信号转导通路阐释栝楼桂枝颗粒的作用机制，分析关键信号分子改变与神经元细胞凋亡之间的相关性，初步筛选出栝楼桂枝颗粒可能作用的分子靶点并进行反向验证。本研究符合中医“整体观念”和中药“整体调节”的特点，将为中药复方治疗缺血性卒中提供新的理论依据。

Traditional Chinese medicines are always employed to treat stroke and post-stroke sequelae. However, the unclear mechanisms and targets still restrict the development of traditional Chinese medicine. The famous preparation Gualou-guizhi decotion is good for the recovery of illness after stroke happening in clinical practice. In the previous study, it is found that Gualou-guizhi decotion has anti-post-ischemia reperfusion injury (MCAO) spasm effect, can inhibit neuronal apoptosis and decrease intracellular Ca2+ concentration, up-regulate the expression of some protein related to calcium signal transduction pathway, suggesting that Gualouguizhi Granule inhibit neuronal apoptosis through regulating of intracellular calcium homeostasis and neurotransmitter balance, thereby activating calcium signal transduction pathway. To carify this mechanism of Gualouguizhi Granule, we intend to develop ischemia reperfusion injury (MCAO) model and NMDA induced neuronal excitability toxicity model, observe the effect of Gualouguizhi Granule combining with MRI multimodal imaging technology. Meanwhile, intend to illustrate the mechanism of Gualouguizhi Granule from calcium signal transduction pathway, and analyse the relation between protein related to calcium signal transduction pathway and neuronal apoptosis. Then use siRNA to validate the target influenced by Gualouguizhi Granule. This study is based on the “holistic concept” of TCM and previous proteomic research with whole characteristic. It will make a new important theory complement to “whole regulation” of Chinese medicine anti- ischemic stroke mechanism.