全脑缺血缺氧损伤是造成心肺复苏后患者死亡的主要原因，而脑内能量代谢与氧化应激异常是全脑缺血缺氧损伤发生的一个重要变化，然而具体的分子机制仍然不清楚。 PDHK1是调控细胞代谢的一个重要分子，它可以通过丙酮酸脱氢酶（PDH）来调节线粒体能量代谢，而线粒体能量代谢与线粒体氧化应激有密切关联。我们前期研究发现，在心肺复苏后全脑缺血缺氧损伤组织中ATP含量显著减低，并且PDHK1表达明显升高。结合文献报道与我们的研究，我们认为在全脑缺血缺氧损伤中PDHK1通过调控线粒体能量代谢和氧化应激发挥重要作用，并且抑制PDHK1将有利于降低神经功能损伤。本课题将利用动物和细胞模型，在分子、细胞和动物水平上揭示PDHK1在心肺复苏后脑缺血缺氧损伤中发挥的重要作用及分子调控机制,并验证DCA（PDHK1抑制剂）对全脑缺血缺氧损伤的保护作用。本课题将为脑缺血缺氧损伤的防治寻找分子代谢靶点，并为药物干预打下基础。

Global brain hypoxic-ischemic injury is the main cause of death in patients with cardiopulmonary resuscitation, and the brain energy metabolism and oxidative stress dysfunction are the important changes after global cerebral hypoxic-ischemic injury. However, the molecular mechanism of brain energy metabolism and oxidative stress dysfunction remain unclear. PDHK1 is an important molecular regulator for cell metabolism, which can regulate mitochondrial energy metabolism through pyruvate dehydrogenase (PDH), and the mitochondrial energy metabolism and mitochondrial oxidative stress are closely linked. Our previous study found that the ATP content was significantly reduced in hypoxic-ischemic brain tissues after cardiopulmonary resuscitation and PDHK1expression was significantly increased. Combined with previous literature and our study, we proposed that PDHK1 play an important role through regulation of mitochondrial energy metabolism and oxidative stress in global cerebral hypoxic-ischemic injury, and inhibits PDHK1 will help reduce neurological damage. This study will reveal the important role and mechanism of PDHK1 in cerebral hypoxic-ischemic injury after cardiopulmonary resuscitation at the molecular, cellular and whole animal levels through animal and cell models, and also verify the protective effect of DCA ( PDHK1 inhibitors) against cerebral hypoxic-ischemic injury. This study will find molecular metabolic target for cerebral hypoxic-ischemic injury and provide the basis for prevention of cerebral hypoxic-ischemic injury.