ERK抑制剂逆调节心肺复苏后脑组织线粒体融合/分裂失衡，抑制神经细胞凋亡机制研究

正常的线粒体融合/分裂对维持线粒体功能稳态和调节细胞生存/死亡至关重要，有学者报道阿尔茨海默病变中细胞凋亡与ERK激活介导的线粒体融合/分裂失衡相关。课题组在前期研究中发现，ERK抑制剂PD98059能使心跳骤停（CA）/心肺复苏（CPR）大鼠脑组织活性氧、Bax和caspase-3表达降低、Bcl-2 表达升高和凋亡细胞数量减少，改善CPR后生存时间和神经功能。CPR后ERK激活介导的脑损伤是否涉及线粒体融合/分裂机制？本项目拟通过CA/CPR大鼠模型和缺糖缺氧再灌注细胞模型实验，采用电镜、生化检测、免疫组化、分子生物学等实验技术，探明ERK抑制剂通过逆调节CPR后由ERK通路介导的线粒体融合/分裂失衡，调整细胞生存与死亡效应蛋白表达的不平衡，阻抑细胞凋亡的分子机制，由此发现CPR后脑保护剂可能的作用靶点，为脑复苏治疗提供新的思路。

The normal mitochondrial fusion/fission is very important for maintaining mitochondrial functional homeostasis and cell survival/death. Scholars reported that cell apoptosis was related to ERK activation mediated mitochondrial fusion/fission in Alzheimer's disease. In the previous study of cardiac arrest (CA) / cardiopulmonary resuscitation (CPR) rat model, our research group found that ERK inhibitor PD98059 could decrease brain tissue oxygen free radicals, Bax and caspase expression, increase the Bcl-2 expression and decrease the number of apoptotic cells, resulting in the improvement of survival time and neurological function after CPR. Is mitochondrial fusion/fission mechanisms involved in ERK activation mediated cerebral injury? This project aims to carry out the experiments of CA/ CPR rats model and sugar-oxygen deficiency-reperfusion cell model, through electron microscope, biochemical detection, immunohistochemical and molecular biology experimental technique, prove the mechanisms of ERK inhibitors on the cell apoptosis inhibition by inversely regulating the unbalanced mitochondria fusion/fission mediated by ERK pathway and adjusting the unbalanced expression of cell survival and death protein after CPR, from that to find the possible targets for brain protective agents after CPR and novel ideas for the treatment of cerebral resuscitation.