心脏骤停后心肌功能障碍（PMAD）是心脏骤停（CA）患者ROSC后早期死亡的关键原因，急性缺血-再灌注损伤（I/R）是导致PMAD的主要因素。乙醛脱氢酶2（ALDH2）是位于线粒体基质内的酶，具有重要的心肌保护作用。有研究显示，心肌发生I/R时，线粒体钙（mCa2+）稳态被破坏，线粒体钙超载进而导致心肌细胞坏死凋亡，而cAMP/PKA可通过调控线粒体Na+/Ca2+交换体（NCLX）增加线粒体钙外排减少钙超载。ALDH2是否通过介导cAMP/PKA通路调控NCLX减少线粒体钙超载、发挥心肌保护作用，目前尚无研究报道。我们前期研究发现，ALDH2激动剂Alda-1可改善大鼠PMAD、增加心肌线粒体钙外排。本课题拟围绕mCa2+超载深入探讨ALDH2在PMAD中发挥心肌保护作用的分子生物学机制，有望为改善PMAD、提高CA患者的出院存活率提供新思路、新靶点。

Post-cardiac arrest myocardial dysfunction or post-myocardial arrest dysfunction (PMAD) is an important cause for early death after ROSC in cardiac arrest (CA) patients, and acute ischemia-reperfusion injury (I/R) is the major cause of PMAD. Aldehyde dehydrogenase 2(ALDH2) is a mitochondrial matrix enzyme that plays a crucial role in myocardial protection. Studies have shown that mitochondrial calcium (mCa2+) homeostasis is destroyed during myocardial I/R, resulting in mitochondrial calcium overload which leads to myocardial cell necrosis and apoptosis. Activation of cAMP/PKA can reduce calcium overload through regulating mitochondrial Na+/Ca2+ exchanger (NCLX) to increase mitochondrial calcium efflux. However, whether ALDH2 could regulate NCLX through mediating cAMP/PKA pathway to reduce mitochondrial calcium overload and play myocardial protection has not been reported in PMAD yet. Our previous study had found that ALDH2 agonist Alda-1 can improve outcome of PMAD in rats and increase mitochondrial calcium efflux. Based on this, we aim to explore the molecular biological mechanism of ALDH2 in PMAD. This project will provide new ideas and target for improving PMAD and increasing the rate of discharge survival of CA patients.