基于脂肪组织-心肌crosstalk探讨omentin改善心功能的作用机制及生脉制剂与活性成分的调节作用

本项目基于心衰发生的中西医病机，结合前期发现益气养阴生脉制剂活性成分人参皂苷显著促进脂肪因子omentin分泌且omentin能保护心肌线粒体功能参与心衰防治的实验证据，提出“生脉制剂及活性成分人参皂苷可能通过调节脂肪组织与心肌组织交叉对话，干预脂肪组织TBK1-AMPK信号途径促进脂肪因子omentin分泌，保护心肌线粒体功能，从而改善心功能防治心衰”的科学假说，拟综合利用抑制剂、激动剂、RNA干扰、CRISPR敲除及过表达技术，及敲除/敲入小鼠模型，进一步确证脂肪因子omentin改善心功能防治心衰的分子机制及其关键调控蛋白，继而深入阐释生脉制剂及有效成分人参皂苷如何干预脂肪与心肌crosstalk发挥心肌保护效应的分子机制，为后期进一步挖掘与临床相关的生物标志物，指导其临床更合理应用提供参考依据，进一步丰富心衰形成的病理机制，为临床心衰的诊断防治和药物研发提供可能的新线索或新策略。

This study is based on the pathogenesis of heart failure in Chinese and western medicine. According to the previous experimental results that bioactive ingredients in ShengMai preparations significantly promote the secretion of omentin in adipose tissue and omentin could protect myocardial mitochondrial function in the prevention of heart failure, we proposed a novel study hypothesis that bioactive ingredients in ShengMai preparations might modulate the crosstalk between adipose tissue and myocardial tissue, promote the secretion of omentin through TBK1-AMPK signaling pathways, and improve heart function via myocardial mitochondrial protection. We would comprehensively use molecular biological techniques (inhibitors, agonists, RNA interference, CRISPR technology and gene overexpression etc), and various models including knockout/knockin mice to find out the key point in which omentin improves heart function and its key regulatory proteins. We expect to elucidate the exact molecular mechanism of bioactive ingredients in ShengMai preparations, for the mediation of crosstalk between adipose and myocardial tissue, so as to provide some evidence for their further clinical application. This research would not only enrich the pathological mechanism of heart failure, but also provide some new clues for drug development for heart failure and investigating the relationship between adipose tissue and cardiovascular diseases.