Nrf2/Bach1-HO1通路调控内皮细胞功能在梯形波胸外心脏按压减轻心肺复苏脑损伤中的作用与机制研究

心脏骤停（CA）是急性死亡的重要死因，提高胸外心脏按压质量降低CA死亡率是亟待解决的世界性难题。近年发现，梯形波胸外心脏按压增加颈动脉血流量、流速，改善脑灌注的效果优于正弦波，但其能否和如何减轻全脑缺血再灌注损伤（GCIRI）尚不完全清楚。课题组近期已发表研究发现，与传统手动按压、正弦波、三角波机械按压相比，梯形波胸外心脏按压明显减轻心肌缺血再灌注损伤，增加冠脉灌注压。预实验结果进一步发现，梯形波胸外按压明显增加大脑皮质Nrf2水平，提示梯形波胸外心脏按压通过降低Bach1竞争性抑制Nrf2的抗氧化/硝化应激作用，调控脑微血管内皮细胞（BMEC）功能，减轻GCIRI。本研究拟采用DCE-MRI、基因敲除等技术，从动物、细胞、分子水平，阐明梯形波胸外心脏按压调控BMEC功能而减轻GCIRI进一步保护神经细胞的机制，为改变心肺复苏按压模式而减轻GCIRI提供实验依据。

Cardiac arrest (CA) is an important cause of acute death. Improving the quality of chest compression to reduce CA mortality is a worldwide difficulty that needs to be solved promptly. In recent years, it has been found that the effect of trapezoidal wave chest compression on increasing carotid arterial blood flow volume and velocity, and improving cerebral perfusion is better than that of sinusoidal wave. However, whether and how it can reduce global cerebral ischemia-reperfusion injury (GCIRI) is not completely clear. A recently published study by our research group found that compared among traditional manual compression, sinusoidal wave and triangular wave mechanical compressions, trapezoidal wave chest compression significantly reduced heart ischemia reperfusion injury and increased. The preliminary experiment results further found that trapezoidal wave chest compression significantly up-regulated the expression of Nrf2 in brain, suggesting that trapezoidal wave chest compression may inhibit oxidative / nitrative stress reactions, regulate brain microvascular endothelial cell (BMEC) function, and reduce GCIRI through Nrf2 protection pathway (such as Nrf2/Bach1-HO1). This study intends to apply DCE-MRI, color Doppler ultrasound, gene knockout and other technologies to elucidate the mechanism, from the animal, cellular and molecular levels, of trapezoidal wave chest compression to regulate BMEC function and reduce GCIRI to further protect neurons, thereby providing experimental evidence of changing cardiopulmonary resuscitation compression mode to reduce GCIRI.