极端环境下意外深低温导致心跳骤停时传统的CPR方法是无效的，ECPB是挽救生命的高级复苏策略，但仍需结合药物治疗以进一步保护神经细胞及线粒体的功能。我们前期的研究显示NHE1抑制剂能上调SIRT3表达，抑制mPTP开放，保护线粒体功能，减轻神经系统损伤，但具体机制仍未阐明。我们推测NHE1介导SIRT3对mPTP结构蛋白CypD去乙酰化的调控起到关键作用。本研究拟应用大鼠深低温心跳骤停ECPB复苏的模型，使用HOE-642抑制NHE1，通过观察SIRT3的表达及对CypD去乙酰化的调控，检测mPTP开放和线粒体的结构与功能，评价复苏后神经系统损伤，揭示抑制NHE1在深低温心跳骤停后ECPB复苏时可以保护神经细胞线粒体的功能，证实经NHE1/SIRT3/CypD通路抑制mPTP开放是其主要机制。本研究将为深低温心跳骤停ECPB复苏后神经细胞线粒体功能的保护提供新思路并奠定相关机制的理论基础。

Traditional CPR is noneffective on accidental deep hypothermia caused cardiac arrest during the extreme environment. ECPB resuscitation is the most effective and advanced strategy in that case. However, the neuronal mitochondrial function still needs further protection by drugs. Our previous studies showed that NHE1 inhibitors can upregulate the expression of SIRT3, inhibit the opening of mPTP, protect the mitochondrial function and reduce the damage of the neurological system, but the exact mechanism remains unclear. We hypothesize that NHE1-mediated SIRT3 plays a key role in regulating the deacetylation of CypD, a structural protein of mPTP. By determining the expression of SIRT3 and its regulation of CypD deacetylation, observing the opening of mPTP and mitochondrial structure and function, and evaluating the neurological function after resuscitation, this study is sought to reveal the protection of inhibiting NHE1 pathway by HOE-642 on mitochondrial structure and function, and confirm NHE1/SIRT3/CypD pathway as the main mechanism of inhibiting the opening of mPTP in the model of accidental deep hypothermia caused cardiac arrest with ECPB resuscitation in rats. This study will offer the new mentality and related theory basis in the protection of neuronal mitochondrial function after ECPB resuscitation on accidental deep hypothermia caused cardiac arrest.