核呼吸因子-1（NRF-1）是DNA转录调节因子，广泛调节由细胞核DNA以及线粒体DNA编码的线粒体呼吸链基因的转录，协调两基因组的表达，改善线粒体氧化呼吸功能，使产能增加，在能量代谢方面起重要作用。近年来研究发现心肌能量代谢异常在心衰的发生发展中起重要作用。我们前期工作也发现重构及衰竭心肌的线粒体氧化磷酸化相关酶表达减少、酶活性降低，线粒体呼吸功能减退、ATP合成减少。因此改善心肌能量代谢可能是心衰治疗的新途径，但能量代谢干预的靶点尚不清楚。本项目设想由于NRF-1是心肌线粒体能量代谢的关键调控因子，靶向上调衰竭心肌NRF-1，可协调并增加线粒体呼吸链相关酶的表达，提高心肌线粒体氧化呼吸功能，增加产能，从而改善心衰患者的预后。本项目从调节能量产生的机制上入手，以改善心肌线粒体能量代谢的新角度来探讨心衰的救治，为心衰治疗提供新的思路和理论基础。

All cellular processes are driven by ATP-dependent pathways. The heart has perpetually high energy demands related to the maintenance of specialized cellular processes. The majority of experimental and clinical studies indicates that the failing myocardium is characterized by changes in energy. ATP is the direct source of energy for all energy-consuming reactions in the heart. Mitochondria provides 95 percent energy for cell activites by oxidative phosphorylation. Since mitochondria are the principal sites of ATP regeneration. Nuclear respiratory factor-1( NRF-1) is a transcriptional activator of nuclear for mitochondria. They regulate most nuclear genes encoding respiratory subunits, factors related to mitochondrial transcription and replication, such as mitochondrial transcription factor A and mitochondrial RNA processing endonuclease, as well as certain heme biosynthetic enzymes. NRF-1 play an important role in coordination of expression of mitochondrial DNA and nDNA. The research in this application will detect the effect of NRF-1 on mitochondria energy metabolism in congestive heart failure induced by coronary artery ligation in rats.