外源性丙酮酸治疗蛛网膜下腔出血后延迟性脑缺血机制研究

蛛网膜下腔出血所致延迟性脑缺血是蛛网膜下腔出血患者死亡或残疾的主要原因，炎症机制介导的血管痉挛可能是引起迟发性脑缺血主要原因。丙酮酸是能量代谢的重要中间产物，外源性丙酮酸已被证实通过抗炎机制及抗谷氨酸神经毒性参与了脑缺血缺氧后神经保护作用。我们研究首次发现，外源性给予丙酮酸能够明显改善蛛网膜下腔出血后延迟性脑血管痉挛动物模型的神经功能障碍并能够改善脑血管痉挛程度。故我们提出丙酮酸及其相关产物可能为治疗蛛网膜下腔出血后延迟性脑缺血的新方向。在此基础上，本课题从血管内皮细胞功能、受体功能及分子生物学方面深入研究丙酮酸参与调解蛛网膜下腔出血后延迟性脑缺血的机制，提出损伤治疗的新靶点和潜在通路，从而为临床开发药物提供良好的应用基础。

Delayed cerebral ischemia resulted from subarachnoid hemorrhage is the main cause of death or disability and inflammation mediated cerebral vasospasm maybe the primary cause. Pyruvate is the important intermediate product in the energy metabolism and exogenous pyruvate has been confirmed that it can protect against ischemic neurologic damage via anti-inflammation and anti-glutamate neurotoxicity mechanism. Our reseach found that exogenous pyruvate could improve the neurologic deficits caused by delayed cerebral vasospasm resulted from subarachnoid hemorrhage. So we propose that the pyruvate and its related products maybe the new direction for the treatment of delayed cerebral ischemia associated with subarachnoid hemorrhage. On the basis of previous research, the project explores the potential mechanism of pyruvate in the treatment of delayed cerebral vasospasm associated with subarachnoid hemorrhage from the point of funtion of vascular endothium, receptor and molecular bilology, proposes new targets and potential pathways for treatment and then supplies application foundation for the development of new drugs.