心肌线粒体辅激活因子PGC-1α与慢型克山病的关系及其分子作用机制研究

It implicates the etiological factor harms the health of the residents, that the younger chronic Keshan disease patients are detected in endemic areas. PGC-1α is a key regulatory factor combining with the transcription factors in myocardial mitochondria biosynthesis and energy metabolism. The abnormal levels of PGC-1α induce the derangements in quantity, morphology and function of mitochondrion, which lead to contractility damage and myocardial hypertrophy, and the cardiomyopathy in the end. Keshan disease is one of mitochondrial cardiomyopathy and pathological changes of the mitochondrion occur earlier and severe. The patients of the chronic Keshan disease in different stages will be investigated to explore the expression of PGC-1α and the coactivator for discovering the path of PGC-1α in heart failure of the chronic Keshan disease.The levels of the factors and the morphous and the function of the mitochondrion will be analysed in primary cultured SD rat myocardial cells treated by low-selenium medium.The aim is to acquire the influence of the selenium deficiency on the mitochondrion in the cardiac muscle, and the results will provide the proof for the mechanism of myocardial damage from selenium defeciency through PGC-1α.

克山病病区低年龄段慢型克山病病例持续检出，提示致病因子仍威胁病区居民的生命健康。PGC-1α是线粒体生物合成和呼吸功能的关键调节因子，通过与转录因子结合发挥调节作用。PGC-1α水平异常，可引起心肌线粒体含量、形态变化和功能受损，导致收缩功能下降、心肌肥大，进而发展为心肌病。克山病属于线粒体心肌病的一种，其线粒体病变具有早发性、严重性的特点。本课题计划对不同病程慢型克山病病例PGC-1α及其共激活因子表达水平的检测，分析慢型克山病心衰中PGC-1α的可能作用路径。并以SD大鼠原代心肌细胞为研究对象，观察低硒作用下心肌细胞PGC-1α表达以及线粒体形态、功能的变化，为低硒通过PGC-1α致慢型克山病心肌损伤的作用机制提供实验室证据。