持续性心肌肥厚引起的心肌重塑是导致心力衰竭重要原因，目前尚缺乏有效方法阻止其进程，其中一个重要原因是心肌肥厚的机制尚未阐明。AMPK激活对心肌肥厚具有重要的保护作用，但其确切作用机制有待进一步阐明，有效激活AMPK的手段有待开发。天然化合物具有多靶点、多途径调控的特点，通过其研究有可能发现新的调控途径、靶点和化合物。前期筛选我们得到有活性的化合物QF84139 (QF)，初步研究发现其可缓解细胞肥大及动物心肌肥厚；机制研究发现其可激活AMPK，但其激活的AMPK在减轻心肌肥厚中的贡献、如何激活AMPK、是否对其它信号通路也有调控作用及确切的作用靶点均有待明确。因此，本项目旨在：1) 明确QF的抗心肌肥厚作用；2) 确定参QF抗心肌肥厚作用的信号通路；3) 揭示AMPK信号通路如何参与QF抗心肌肥厚的作用；4) 探寻QF的直接作用靶点和功能。研究发现将揭示心肌肥厚调控和干预的新机制、新靶点。

Prolonged hypertrophy leads to cardiac remodeling, resulting in heart failure, which is a major cause for the increased mortality of cardiovascular diseases. Current approaches for clinical treatment of myocardial hypertrophy is still limited. Activation of AMP-activated protein kinase (AMPK) signaling pathway has been shown to play an essential role in anti-cardiac hypertrophy effect. There is a growing interest in exploring effective cardioprotective components extracted from Traditional Chinese Medicine, because they have been practiced for thousands of years and present multi-targets and multi-channel characteristics of cardioprotection. Through the screening, we found that a chemical compound QF84139 has anti-cardiac hypertrophy effects in phenylephrine-induced cardiomyocyte hypertrophy and transverse aortic constriction-induced cardiac hypertrophy. In addition, we found that AMPK signaling pathway is activated by QF84139. However, it is unclear how big contribution of activated AMPK to the effect of QF84139 in anti-cardiac hypertrophy, how AMPK is activated by QF84139, whether any other signaling pathways are involved in the effect of QF84139, and what is the direct target of QF84139 in the effect of anti-cardiac hypertrophy. To address these questions, the present study aims to: 1) characterize the anti-cardiac hypertrophy effects of QF84139; 2) elucidate the protective mechanism and involved signaling pathways of QF84139; 3) determine how AMPK signaling pathway involved in the effects of QF84139 in anti-cardiac hypertrophy; and 4) identify the direct cellular target of QF84139. Our data will provide new insight into the mechanisms of pathological hypertrophy and provide new intervention targets for cardiac remodeling.