CIRP调控线粒体相关内质网膜（MAM）钙离子转运在低温脑复苏中的作用及机制研究

心跳骤停后全脑缺血再灌注损伤严重影响心肺复苏后患者的生存率及神经功能预后。寻找新的有效的治疗缺血再灌注损伤的靶点是目前研究的热点与难点。前期研究中我们发现冷诱导RNA结合蛋白（CIRP）具有神经元复苏作用，但是具体的作用机制还不清楚。鉴于（1）线粒体相关内质网膜（MAM）调控的钙离子可维持线粒体正常能量代谢；（2）脑缺血再灌注损伤会导致MAM调控的线粒体内钙超载，能量失衡；（3）低温诱导的CIRP被抑制后可加重线粒体损伤诱导的细胞凋亡。结合预实验结果，CIRP可以同MAM中钙离子转运复合体相互作用。我们推测：低温诱导的CIRP可能通过抑制MAM中钙离子的转运，降低线粒体内钙超载进而改善线粒体能量代谢，发挥神经元复苏作用。本研究通过在体和离体实验，利用分子生物学等技术，从整体-细胞-细胞器-分子-离子等多角度揭示低温诱导的CIRP的神经元复苏机制，为提高脑复苏成功率提供新思路。

Global cerebral ischemia-reperfusion injury resulted from cardiopulmonary resuscitation (CPR) seriously affects the survival rate and neurological function prognosis of patients with cardiac arrest. It is a hot topic to study the mechanism of ischemia-reperfusion injury and find a new way to alleviate it. 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommended, comatose patients with out‑of‑hospital ventricular fibrillation cardiac arrest were cooled to 32–34°C for 12 or 24h. Therapeutic hypothermia is an effective intervention. In our previous studies, we found that the cold induced RNA binding protein (CIRP) has a protective effect on cerebral. However, the detailed mechanism is unclear. Inview of (1) Calcium regulated by mitochondria associated endoplasmic reticulum membranes (MAM) can maintain normal mitochondrial energy metabolism;(2) Cerebral ischemia/reperfusion injury can lead to calcium overload and energy imbalance in mitochondria regulated by MAM; (3) Inhibition of CIRP can aggravate mitochondrial injury-induced apoptosis. Combined with pre-experiment results: CIRP can interact with the calcium transport complex IP3R-GRP75-VDAC1 in MAM. We speculate that CIRP may affect calcium transport complex in MAM, inhibit calcium transport, reduce calcium overload in mitochondria, improve mitochondrial energy metabolism, and play a role in neuronal resuscitation. In the research, we create ischemia-reperfusion model in vivo and vitro to simulate clinical cardiac arrest of cerebral injury patients. We take the relationship between CIRP and MAM which regulate the calcium transport as the entry point in order to reveal the mechanisms of hypothermia induced CIRP resuscitating neuron through whole body-cell-organelle-molecule-ion. We hope it can provide a new target for improving the successful rate of cerebral resuscitation.