醒脑静调控活性氧—自噬交互作用干预脑卒中急性期神经血管单元损伤的机制

活性氧和自噬在维持细胞存活及稳态方面有重要作用，出血性及缺血性脑卒中早期均存在不同程度的激活，如何适度调控活性氧与自噬及交互作用是目前脑卒中研究的重点之一。临床实践证明醒脑静在急性期未能进行影像学评价，不能明确诊断出血和缺血性质时，具有早期干预优势。本研究采用大鼠局灶性脑缺血再灌注模型和自体血注入脑出血两种动物模型，同时结合神经细胞、胶质细胞、内皮细胞共培养体外模拟神经血管单元模型，针对脑卒中损伤早期激活的活性氧诱导自噬的ROS-HIF1-BNIP3/NIX分子信号通路及自噬对活性氧的反馈作用，采用激光共聚焦免疫双标、影像学评价、电镜、分子生物学等方法，综合分析醒脑静通过调控活性氧和自噬的适度活化及交互作用维持细胞内稳态保护神经血管单元的途径和机制，为在“病络—毒损脑络”理论指导下，中医药早期干预出血和缺血性中风病提供理论基础和实验依据。

ROS and autophagy have an important role in maintaining cell survival and the homeostasis, they can be activated of different degrees in early acute brain injury, such as cerebral hemorrhage and cerebral ischemia. The interaction between ROS and autophagy has become one of the focuses in current stroke research. Clinical practice has proved that Xingnaojing, without restriction of radiological conditions on the treatment, reflects the advantages of early intervention. This study uses two types of animal models, the MCAO model and the cerebral hemorrhage model by injecting autologous blood in brains of rats, combining with neurovascular unit model that nerve cells, glial cells, endothelial cells in vitro co-culture simulate, pointing at the important pathological aspects during the early damage of cerebral ischemia and cerebral hemorrhage – the activation of ROS-HIF1-BNIP3/NIX-Autophagy molecular signal pathway and regulation of autophagy on ROS, uses laser confocal immune double staining method, MRI, electron microscopy, molecular biology and enzyme immunoassay methods from both in vivo and in vitro aspects comprehensively to explore the mechanism of XNJ protect the neurovascular unit by regulating the interplay between ROS and autophay. This study will provide a theoretical basis for Chinese medicine interventing the early stage of acute ischemic and hemorrhagic stroke under the theoretical guidance of " abnormal collateral - toxin damage brain collaterals ".