结合多模态影像技术观察VDAC1介导氢气对CA-ROSC兔脑能量代谢的作用及机制研究

According to the Resuscitation Outcomes Consortium, the frequency of cardiopulmonary resuscitation (CPR) is growing. As a result, the number of patients with severe neurological deficits post-restoration of spontaneous circulation (ROSC) has steadily increased. Cardiac arrest (CA) still carries a very poor prognosis after ROSC by successful resuscitation. How to reduce cardiac neurological dysfunction is the key and difficult points of cardiopulmonary cerebral resuscitation. We had found that hydrogen intervention CA animal models could decrease of brain neurons apoptosis and improve neurological function. At the same time, we found that hydrogen could reduced mitochondrial membrane voltage-dependent anion channel 1 (voltage-dependent anion channel l, VDACl) protein expression. VDAC 1 is an important component of the mitochondrial permeability transition pore (PTP), which is closely related to the mitochondrial energy metabolism, mitochondria-mediated apoptosis. So we hypothesized that hydrogen may play a protective role in energy metabolism through VDAC1. We plan to use rabbit cardiac arrest model to observe the effect of energy metabolism by hydrogen through the multi-modal imaging techniques include magnetic resonance spectroscopy (MRS) and PET/CT detect. Then we explore the further mechanism of hydrogen effects on energy metabolism by gene transfection, RNA interference by cell culture. We hope can help to provide a theoretical basis and foundation for the clinical application of hydrogen through this study.

心搏骤停(CA)后神经功能障碍是影响复苏后自主循环恢复(ROSC)患者预后的重要原因，我们前期研究发现氢气干预CA-ROSC动物模型可以减少脑神经元凋亡并改善神经功能，同时发现氢气下调了线粒体膜电压依赖性阴离子通道1(VDAC1)蛋白的表达，而VDAC1是线粒体通透性转运孔 (mPTP)的重要成分，与线粒体能量代谢和线粒体介导的细胞凋亡密切相关。由此我们推论：氢气可能通过VDAC1-线粒体途径影响脑细胞能量代谢而发挥保护作用。本项目拟在前期已建立的兔CA-ROSC模型基础上，采用磁共振波谱(MRS)和PET/CT相结合的多模态影像技术无创、动态观察氢气对脑细胞能量代谢的影响，并采用基因转染、RNA干扰等多种手段干预神经细胞VDAC1表达，观察细胞能量代谢变化，结合体外和体内实验验证上述推论，为应用氢气治疗CA-ROSC患者提供理论基础和实验依据。