硫化氢对心跳骤停复苏后血脑屏障的影响及PKC-TJ通路在其中作用的研究

调控和维持血脑屏障（BBB）完整性是改善患者心跳骤停复苏后神经功能转归的棘手难题。H2S是近期被发现的第三类气体信号分子，研究证实H2S在减轻神经功能损伤和改善神经功能转归方面具有重要的调节作用，但H2S对BBB的影响和内在机制尚不清楚，国内外研究较少。我们前期的研究显示，心肺复苏后BBB的破坏与复苏后脑水肿含量的增加、神经元的凋亡和神经功能的缺陷密切相关。80ppmH2S能减轻BBB损伤后FITC-dextran的渗漏，减少电镜下紧密连接（tight junction, TJ）的破坏和基底膜的断裂，并改善神经功能转归。本项目在此基础上利用大鼠心跳骤停复苏模型，从PKC蛋白家族及TJ表达、组织学及功能学等方面探讨H2S对心肺复苏后BBB的影响及H2S-PKC-TJ信号通路在其中的作用及调控机制。以期寻找一种能改善心肺复苏后患者神经功能转归的新途径，进而为H2S的临床应用提供重要的理论基础。

Adjusting and maintenance of the integrity of blood brain barrier (BBB) is one of the most difficulty problem to improve the neurological function after cardiac arrest and resuscitaion.Recent researchs demonstrated that as the third gaseous signaling molecule, hydrogen sulfide (H2S) played an important role in reducing and ameliorating the damagement of neurological function. However, there is rare report about the effect of H2S on BBB and the underlying mechanisms. In our previous study, we found that the damagement of BBB after cardiac arrest is closely related to the brain edema, neuron apoptosis and neurological function deficit. Inhaling of exogenous 80ppm H2S reduced the permeability of FITC-dextran,the damagement of tight junction (TJ), the fracture of basement membrane and improvement the neurological function. In this program, we will explore the effects of H2S on BBB using the cardiac arrest and resustitation model in rats.The expression of PKC protein family and the TJ, the changes of histology and the neurological function will be studied. Moreover, we will testify whether the H2S-PKC-TJ signal pathway is one of the mechanisms using this in vivo studies. These findings will give us a new idea and a new target point for portection of BBB, which will establish a theoretical base for the clinical application of H2S.