脑卒中是目前中国人疾病死亡第一位原因，缺血性脑卒中是最常见的脑卒中类型，但临床治疗效果并不十分理想，其主要原因在于缺血性脑卒中的损伤机制尚不完全清楚。泛素C末端水解酶L1(UCH-L1)和经典型蛋白激酶C(cPKC)gamma均为神经元特异性蛋白，我们也初步发现二者均参与脑缺血损伤，并存在相互作用。在此基础上，本研究拟利用cPKC gamma基因敲除小鼠、大脑中动脉阻塞(MCAO)致缺血性脑卒中和神经元氧-糖剥夺(OGD)缺血模型，借助荧光共振能量转移、siRNA干扰、泛素K48/K63和UCH-L1定点突变等技术，明确UCH-L1通过cPKC gamma调节脑缺血损伤的作用及其分子机制，从而丰富人们对缺血性脑卒中损伤机制的认识，并为临床治疗提供新的药物作用靶点。

Stroke is the first cause of the Chinese disease death. Ischemic stroke is the most common type of stroke, but its clinical therapeutic effect is not ideal. The main reason is that the injury mechanism of ischemic stroke is not fully clear. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and classical protein kinase C (cPKC) gamma are neuron-specific proteins. Our preliminary results found that UCH-L1 and cPKC gamma interacted with each other, and both of them participated in the cerebral ischemic injury. On this basis we will explore the role of UCH-L1 in ischemic injury and its regulatory mechanism on cPKC gamma in this study, using cPKC gamma knockout mice, cerebral artery occlusion (MCAO) induced ischemic stroke and oxygen-glucose deprivation (OGD) ischemia models. The techniques of fluorescence resonance energy transfer, siRNA interference, ubiquitin K48/K63 and UCH-L1 site-directed mutation will be used. The results obtained will enrich people's knowledge on injury mechanism of ischemic stroke and provide new drug targets for its clinical treatment.