基于PGC-1α/HIF-1α通路介导的血管内皮线粒体能量代谢探究抑郁症“气虚脉损”的生物学实质及中药防治机理

抑郁症已成为重大社会疾病，并且会促进动脉粥样硬化的发生发展，血管内皮损伤是抑郁症导致动脉粥样硬化的关键环节。本课题组前期研究发现线粒体功能障碍是抑郁症以及抑郁导致血管内皮损伤的重要机制，结合线粒体功能异常与中医“气虚证”表现相似的特点，创新性提出抑郁症“气虚脉损证”，并选择对线粒体生物合成及血管内皮功能均具有重要调节作用的PGC-1α/HIF-1α通路作为研究靶点。首先拟通过临床研究，探究患者抑郁程度与血管内皮损伤水平的关联性；然后通过动物实验，基于PGC-1α/HIF-1α通路动态探究抑郁大鼠血管内皮损伤的演变机制及醒脾解郁方防治作用；最后通过细胞实验，进一步揭示醒脾解郁方对PGC-1α/HIF-1α通路的调控机制及作用靶点。期待阐明PGC-1α/HIF-1α通路介导的血管内皮线粒体能量代谢异常是抑郁症“气虚脉损”的生物学实质之一，为中药防治抑郁症血管内皮损伤提供新的理论依据及方药支持。

Depression has become a major social disease, and will promote the occurrence and development of atherosclerosis, vascular endothelial damage is the key link of depression leading to atherosclerosis. Our previous study found that mitochondrial dysfunction is an important mechanism of depression and vascular endothelial damage caused by depression, combined with the similar characteristics of mitochondrial dysfunction and "Qi deficiency syndrome" of traditional Chinese medicine, we innovatively put forward the "Qi deficiency damage vessels syndrome" of depression, and selected the PGC-1 α / HIF-1 α pathway, which plays an important role in the regulation of mitochondrial biosynthesis and vascular endothelial function, as the research target. First of all, through clinical research, to explore the relationship between the degree of depression and the level of vascular endothelial injury; then through the animal experiment, based on the PGC-1 α / HIF-1 α pathway, we explored the evolution mechanism of vascular endothelial injury in depression rats and the preventive and therapeutic effects of Xingpi Jieyu Fang; finally, through cell experiments, to further reveal the regulatory mechanism and target of Xingpi Jieyu Fang on PGC-1α / HIF-1α pathway. It is expected to clarify that the abnormal energy metabolism of vascular endothelial mitochondria mediated by PGC-1α / HIF-1α pathway is one of the biological essence of "Qi deficiency damage vessels" in depression, and provide a new theoretical basis and prescription support for the prevention and treatment of vascular endothelial injury in depression by traditional Chinese Medicine.