随着人口老龄化及手术多样化，脑缺血再灌注损伤的预防及诊治已成为现代围术期医学中的重要课题。我们的前期研究发现COX抑制剂阿司匹林可抑制脑缺血再灌注后的中枢炎性反应，改善神经功能损伤，但调节神经炎性的具体机制未明。基因芯片及蛋白质互作网络分析显示趋化因子CXCL1/CXCR2与脑缺血再灌注损伤及中枢炎性反应具有密切相关性。本项目拟在前期研究的基础上，利用MCAO大鼠模型及小胶质细胞氧糖剥夺损伤模型，以不同剂量的高选择性COX-2抑制剂为干预措施，通过在体与离体实验，采用神经功能、行为学、形态学、分子生物学等综合方法，探讨及验证COX-2抑制剂对围术期脑缺血再灌注损伤的保护作用以及趋化因子CXCL1/CXCR2在其中的调控机制。不仅为高选择性COX-2抑制剂的围术期临床应用提供可靠的研究基础，而且为进一步研发调控神经炎性反应的脑保护药物提供了新的靶点。

To explore the protective methods of cerebral ischemia-reperfusion injury is an important task of modern perioperative therapy with aging of population and diversification of operation. In the previous studies, we observed that the neuroprotection of COX inhibitor aspirin was depended on the regulation of neuroinflammation. However, the mechanism remains unclear now. Furthermore, the informations based on differentially expressed gene microarrays and protein-protein interaction network show chemokine pathway CXCL1/CXCR2 plays a key role in the cerebral ischemia reperfusion injury and the development of neuroinflammation. Our preliminary trials showed that COX inhibitor restrained the activation of microglia and the releasing of inflammatory factors. Based on the previous studies, we are going to further investigate the role and mechanism of chemokine pathway CXCL1/CXCR2 on the protective effects of COX-2 inhibitor on perioperative cerebral ischemia reperfusion injury. MCAO model is used to simulate the perioperative brain ischemia reperfusion injury and the oxygen glucose deprivation model of microglia is used to measure the chemotaxis of CXCL1. Different doses of COX-2 inhibitor are administered as intervention to evaluate the expressions of target biomarkers via neurofunction, behavioristics, histology and molecular biology. The expected results of this study is to verify that COX-2 inhibitor improve the neurological function and decrease cerebral inflammatory response after cerebral ischemia reperfusion injury via CXCL1/CXCR2 pathway, which will not only provide the research foundation for the clinical use of COX-2 inhibitor, but also lead to novel targets for developing neuroprotective drugs via the modulation of neuroinflammation.