中文摘要
心力衰竭代谢重构以线粒体结构功能损伤为核心,线粒体既是心力衰竭时病理因子攻击的靶标,也是心力衰竭时各种病理变化的起源。前期发现参附方心血管保护作用与改善心脏能量代谢和线粒体功能有关,本课题在饮片、组分、成分三个层次,在临床、动物、细胞、分子四个水平,考察参附配伍对心力衰竭心脏能量代谢重构、线粒体结构和功能、心室重塑等指标的影响,重点研究参附配伍对心肌细胞中PGC-1α/ERR相关通路的影响,从PGC-1α/ERR通路探索乌头碱与人参皂苷配伍的减毒增效机制。明确参附方改善心肌能量代谢的信号传导通路和关键调控因子,发现参附方作用的关键生物标志物和作用靶点,基于作用靶点构建筛选体系,发现参附方改善慢性心力衰竭心脏能量代谢重构的效应组分,进行组分中药的成药性研究。课题研究为中药二次开发,组分配伍新药提供有效支撑。
英文摘要
Mitochondrial function played important roles in metabolic remodeling of cardiac failure, mitochondria was attacked by pathology factor of cardiac failure, and mitochondria was also genesis of cardiac failure. In the previous study, the function of shenfu fang involved in energy metabolism and mitochondrial function. The effects of shenfu fang on metabolic remodeling and PGC-1α-ERR pathway in heart failure rats were investigated, the effects of shenfu fang on mitochondrial structure and function were observed, the effects of shenfu fang on mitochondrial permeability transition pore, energy metabolism, activity of respiratory chain, Ca2+ overload, reactive oxygen species, apoptosis, autophagy on mitochondria were also studied. The compatibility mechanism of aconitine and saponin of red ginseng were clarified based on the PGC-1α/ERR pathway. The role of the pathway and target of shenfu fang in metabolic remodeling was identified. Screening platform based on target was established, active components of shenfu fang were discovered, new drug based on active components were studied. The data will help new herbal drugs development and renew the old drugs.
