抑制过度自噬或激活AMPK可抑制病理性心肌肥厚及其向心衰转化。申请人在前期国家自然科学基金支持下，发现一种小分子化合物DMH1具有抗病理性心肌肥厚、抑制自噬和激活AMPK的作用，因此提出研究课题：一种新型自噬抑制剂及其抗病理性心肌肥厚机制研究，主要内容包括：(1)DMH1抑制自噬作用及机制；(2)DMH1激活AMPK通路的具体靶点；(3)DMH1抑制自噬作用与抗病理性心肌肥厚作用关系；(4)DMH1激活AMPK与抗病理性心肌肥厚作用关系；(5)DMH1对心肌能量代谢、线粒体功能的影响及与抗病理性心肌肥厚的关系。以上研究以DMH1同类结构药物compound C和DMH4作为参照。本课题最终目标并不仅是研究DMH1的作用及机制，而是通过对DMH1,DMH4, compound C的比较研究，阐明此类药物的作用机制、确定先导结构，为新型抗心肌肥厚/心衰药物和新型自噬抑制剂的开发奠定基础。

Inhibition of excessive autophagy or activation of AMPK can inhibit pathological heart hypertrophy and the subsequent heart failure. Based on the support of previous NSFC foundation, we found a small chemical DMH1 that exerted the effects of antagonizing pathological heart hypertrophy, inhibiting autophagy and activating AMPK, therefore, we put forward the present project: a novel autophagy inhibitor and its mechanism of inhibiting pathological cardiac hypertrophy. The content of the project includes: (1) The autophagy inhibition and the underlying mechanism of DMH1. (2) The targets of DMH1-induced AMPK pathway activation. (3) The relationship between DMH1-induced autophagy inhibition and the antagonizing heart hypertrophy; (4) The relationship between DMH1-induced AMPK activation and the antagonizing heart hypertrophy; (5) The effects of DMH1 on cardiac energy metabolism, mitochondrial function and the relationship between these effects and the antagonizing heart hypertrophy. We use compound C and DMH4, the analogous structure chemicals of DMH1, as the comparison. The purpose of the project is not only to study of the effects of DMH1 and its underlying mechanism, but, through the comparison of DMH1,DMH4, and compound C, we aim to elucidate the action mechanism of this type of drugs and identify the structure of the leading compounds, establishing the basis for developing a novel type of anti- heart hypertrophy drugs and novel autophagy inhibitor.