细胞外信号调节激酶ERK通路在大麻素受体激动剂WIN55，212-2心肺复苏后脑保护作用中的调控机制研究

脑缺血再灌注损伤是导致心肺复苏（CPR）后远期存活率下降的重要原因之一，多种脑保护措施的综合干预有助于改善预后。我们前期研究发现大麻素受体激动剂WIN55，212-2在心肺复苏后可诱导低温并改善大鼠的神经功能。药理研究显示WIN55，212-2还具有抗炎、抗凋亡等作用，有利于减轻缺血再灌注损伤，其作用可能与受体激活细胞外信号调节激酶（ERK）有关。因此，我们设想该药除低温效应外还可能通过其它作用改善心肺复苏的预后。本研究拟在前期研究的基础上，建立大鼠心脏骤停模型，通过用物理方法阻断WIN55，212-2的低温效应，，观察其在CPR后是否仍具有神经保护功能，并应用大麻素受体拮抗剂及ERK抑制剂，观察受体效应、ERK通路的激活、与其相关的大脑细胞凋亡及DNA修复情况，探索WIN55，212-2是否通过其受体激活ERK通路介导神经保护作用。研究将为该类药物应用于心肺复苏后脑保护提供一条新思路。

Cerebral ischemia/reperfusion, as one of the important factors, result in short survival after cardiopulmonary resuscitation (CPR). multiprotection will improve susvival.We demonstrated cannabinoid receptot agonist WIN 55212-2 [4,5-Dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenylcarbonyl)-6H-pyrrolo[3,2,1-i,j]quinolin-6-one] induced hypothermia after CPR, improved the neurologically function and prolonged survival. WIN55,212-2 was antiinflammatory and antiapotosis as well, which was related with it's receptor activting extracellular signal-regulated kinase (ERK). Therefore, we hypothesized WIN55,212-2 might improve neurologic function via other mechanism including hypothermia after CPR. In this project, we will establish cardiac arrest (CA) model in rat, to investigate the effect of WIN55,212-2 under normothermia after CPR. And animals will be treated with CB1 or CB2 antagonist or inhibitor of extracellular signal-regulated kinase(ERK),we will observe whether the neuroprotection effect of WIN55,212-2 is regulated by the progression of CB1 receptor-mediated ERK activation after CPR. The results will provide a new thought for cerebral protection after CPR.