病理性心肌肥厚早期，心肌线粒体受损，且PINK1/Parkin介导的线粒体自噬水平升高，miRNA-34可能参与调节Parkin表达与线粒体功能。因此我们提出假设：PINK1/Parkin介导线粒体自噬参与病理性心肌肥厚的发病，miRNA-34是上述通路的调控分子。本研究首先采用组织学与分子生物学方法，揭示病理性心肌肥厚进展中PINK1/Parkin通路、线粒体自噬水平时序性变化规律；其次，采用基因技术改变Parkin基因表达，分析PINK1/Parkin通路活性及线粒体自噬水平对线粒体和心脏结构功能变化的影响，首次证实其在病理性心肌肥厚发展中的作用；最后，以miRNA-34为着眼点，探索PINK1/Parkin通路介导线粒体自噬的上游调控机制。本研究不仅可丰富病理性心肌肥厚发病的分子机制，且为以线粒体自噬为靶点，从线粒体质控角度防治病理性心肌肥厚提供理论基础，也为心衰精准防治提供新途径。

In the early stage of pathological myocardial hypertrophy, there are myocardial mitochondria injury, and the level of mitophagy mediated by PINK1/Parkin is increased. MiRNA-34 may be involved in regulating the expression of Parkin and the mitochondrial function. Therefore, we hypothesized that mitophagy mediated by PINK1/Parkin is involved in the pathogenesis and development of pathological myocardial hypertrophy, and MiRNA-34 is an important regulator of PINK1/Parkin pathway. In this study, we first used histology and molecular biological methods to reveal whether there is a sequential change in PINK1/Parkin pathway activity and mitophagy level in pathological myocardial hypertrophy. Secondly, we analyze the impact of PINK1/Parkin pathway activity and mitophagy level on the structure and function of myocardial mitochondria and the heart, by using the technology of gene transfection and gene silencing to change the expression of Parkin, for the first time to confirm that the mitophagy mediated by PINK1/Parkin pathway plays a key role in the initiation and development of pathological myocardial hypertrophy; Finally, at the point of miRNA-34, we explored the upstream molecular regulation mechanism of mitophagy mediated by PINK1/Parkin pathway. The results of the project will not only enrich the molecular mechanism of pathological myocardial hypertrophy, but also provide a solid theoretical foundation for the prevention and treatment of pathological myocardial hypertrophy from the perspective of mitophagy and mitochondrial quality control, and it is also expected to be a new way for precision prevention and treatment of heart failure.