高尔基体在脑出血后继发性脑损伤中的作用及机制研究

继发性脑损伤是脑出血病情进展的主要原因，它的机制主要包括炎症、氧化应激及血脑屏障损伤及细胞死亡通路。我们前期研究在缺血性脑损伤中发现高尔基体出现不同程度的碎裂，并且在体外缺氧模型中证实高尔基体通过其应激蛋白GOLPH3直接影响细胞内氧自由基的生成。结合其他研究发现高尔基体能调节血脑屏障通透性和介导炎症相关因子TLR4的迁移和激活，我们推测高尔基体能通过介导氧化应激、炎症、血脑屏障的损伤参与脑出血后继发性脑损伤。因此，在本研究拟从体内和体外实验研究脑出血后高尔基体形态结构功能变化，深入探讨GOLPH3在脑出血后氧化应激、炎症、血脑屏障破坏中的作用及其可能的机制，为脑出血的临床治疗提供潜在的靶点。

Secondary brain injury is the main cause for the deterioration of intracerebral hemorrhage (ICH). Inflammation, oxidative stress, blood-brain barrier damage and cell death pathway play important roles in the secondary brain injury. We previously found that Golgi apparatus showed different degrees of fragmentation in animal models of ischemic brain injury，and further proposed that GOLPH3 was a Golgi stress protein and demonstrated Golgi can directly affect cellular ROS production via regulating the expression of GOLPH3 in a model of oxygen glucose deprivation reperfusion. Additionally, researchers also found that Golgi apparatus can affect the permeability of the blood-brain barrier and mediate the migration and activation of TLR4. Based on all these preliminary findings, we speculate that the Golgi apparatus may participate in oxidative stress, inflammation, and the disruption of the blood-brain barrier after ICH. Therefore, in this study, we will study the morphological and structural changes of Golgi after ICH in vivo and in vitro, explore the role and mechanism of Golgi stress protein GOLPH3 in secondary brain injury as well as the related signaling pathway. The successful implementation of this project will help to expand the understanding of the mechanism of secondary brain injury after ICH, and provide a potential target for the clinical treatment of ICH.