静脉麻醉药物丙泊酚通过NADPH氧化酶通路对脑出血的保护作用及机制的研究

项目名称： 静脉麻醉药物丙泊酚通过NADPH氧化酶通路对脑出血的保护作用及机制的研究

项目编号： No.81473285

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 赵晓春

作者单位： 中国医科大学

项目金额： 55万元

中文摘要： 脑出血是重症病房一类严重的中枢神经系统急症。新型静脉麻醉药丙泊酚除广泛应用于各种手术麻醉外，已成为脑损伤患者镇静的首选药。NADPH氧化酶(Nox)是细胞内活性氧产生的最主要系统，参与脑出血后的脑损伤，但机制尚不清楚。研究表明丙泊酚可以抑制脑挫裂伤中Nox的激活产生脑保护作用。前期研究表明，丙泊酚对脑出血有保护效应，并且抑制了脑出血后Nox的活性。因此我们推测丙泊酚可能是通过抑制Nox，进而对脑出血后脑水肿、炎症反应、自噬、神经血管偶联和白质损伤发挥保护作用的。我们首先明确脑出血中丙泊酚的作用效果和作用方式，观察其对脑出血后各种病理生理变化的影响；其次研究Nox通路的激活对脑出血的作用和机制；再次观察丙泊酚的脑保护效应与Nox通路激活的关系及可能的机制；最后联合低温脑保护，观察丙泊酚结合Nox抑制剂对脑出血的治疗效果。该研究将为丙泊酚的临床治疗应用奠定理论基础，为脑出血的治疗提供新途径。

中文关键词： 麻醉药物；丙泊酚；NADPH氧化酶；脑出血

英文摘要： Intracranial hemorrhage is the most lethal type of central system disease.Propofol is a kind of general intravenous anesthetic widely used in many kinds of surgery and has been the fist choice to sedate the brain trauma patients. NADPHase (Nox) is the main system to produce reactive oxygen, compromise in the ICH. But the mechanism is still not clear yet. Studies show that propofol could produce protective effect in the traumatic brain injury by inhibiting the activity of the Nox. Our preliminary data showed that propofol could protect the brain from hemorrhage stroke by inhibiting the activated Nox. So we hypothesized that propofol could inhibit the Nox then supress the brain edema, inflammation, autophage, neurovascular coupling and white matter injury. We will first illustrate the effects and mechanism of the propofol in the hemorrhage stroke by investigating the pathophysiological changes after stroke; then reveal the relation between activated Nox and hemorrhage stroke; thirdly, find the relation between protective effect of propofol and Nox activating signal pathway; forthly, adjunctive use of hypothermia, to investigate the effect of combinating use of propofol and Nox inhibitor in treating the hemorrhage stroke. This study will provide a solid mechanism foundation for clinical use of propofol and find new way to treat hemorrhage stroke.

英文关键词： anaesthetics;propofol;NADPH oxidase;intracranial hemorrahge