基于线粒体炫探讨益气活血中药调控心衰心肌细胞ATP稳态的机制研究

线粒体炫是近年来发现的一种新的线粒体动态变化现象，可以调控心肌细胞ATP的稳态，是线粒体能量代谢的生物标志物，其触发受到线粒体内膜标志物抗增殖蛋白PHBs的调控。线粒体炫频率异常可加剧心衰的病程。本课题组前期研究证实益气活血中药心复康口服液是治疗心衰的有效中药，通过调节线粒体能量代谢重构，增加ATP合成，改善心功能。通过对心衰心肌线粒体亚群的内膜蛋白的研究发现，心复康口服液可以显著上调PHBs表达。因此我们推测该药对维持心衰心肌细胞线粒体炫频率正常化有一定作用。本研究拟以PHBs和线粒体呼吸链超复合物（mitoSC）为研究对象，以线粒体炫现象为切入点，利用mt-cpYFP转基因小鼠及各种分子生物学技术，对心衰时线粒体能量代谢的动态变化进行全面研究。阐明心复康口服液对心衰心肌线粒体能量代谢稳态调节的分子机制和效应靶点，为心衰的代谢治疗开辟新的途径。

The mitochondrial flash (mitoflash) is a newly discovered dynamic activity of the mitochondria, which can regulate ATP homeostasis in the myocardial cells, and is a novel biomarker of mitochondrial energy metabolism. Mitoflash occurrence is regulated by prohibitins (PHBs), which is a marker of inner membrane of mitochondrial (IMM). The abnormal frequency of mitoflash can aggravate the process of heart failure (HF). The previous researches of our team had confirmed that the Yiqihuoxue traditional Chinese medicine (TCM) Xinfukang decoction was effective for treating HF. Xinfukang can increase ATP synthesis and improve heart function through regulating the reconstruction of mitochondrial energy metabolism. From the study on the proteins of IMM subsets of HF myocardium, we found that Xinfukang decoction can significantly increase the expression of PHBs. Therefore, we speculate that the drug has a certain effect in maintaining the normalization of mitoflash in HF cardiomyocytes. This study intends to take PHBs and mitoSC as the research objects and take the mitoflash phenomenon as the entry point, using mt-cpYFP transgenic mice as well as various molecular biological techniques to comprehensively study the dynamic changes of mitochondrial energy metabolism during HF. Our aim is to clarify the molecular mechanism and effect targets of Xinfukang decoction on the regulation of HF myocardial mitochondrial energy metabolism and to open a new way for the metabolic treatment of HF.