苓桂气化方通过AngⅡ/TGF-β1/Smads信号通路干预射血分数保留心衰的机理研究

射血分数保留心衰（HFpEF）发病率逐年增加，占心衰总数的半数以上，其发病机制与治疗是目前临床的难点。研究表明， AngⅡ/TGF-β1/Smads信号通路是介导心房纤维化的重要机制，而心房纤维化是HFpEF的核心病理环节。我们前期研究发现，在HFpEF动物模型成功建立基础上，苓桂气化方能明显改善心脏的舒张功能和心房纤维化，但机理不清楚。据此提出假说：AngⅡ/TGF-β1/Smads是促发HFpEF进展的重要信号通路，苓桂气化方可通过调控该通路改善HFpEF。为验证这一假说，我们将通过建立多因素复合HFpEF动物模型，采用生物信息学、分子生物学、斑点超声技术等手段，从相关因子的蛋白、基因表达，明确AngⅡ/TGF-β1/Smads信号通路在HFpEF发生中的作用，阐释苓桂气化方干预该通路的效应机制，进而揭示HFpEF的发生机制与中药干预途径，为中医药防治HFpEF提供实验依据。

The incidence rate of heart failure with preserved ejection fraction (HFpEF) increases year by year, accounting for more than half of the total heart failure. The pathogenesis and treatment of HFpEF are the difficulties in clinic. The results show that atrial fibrosis mediated by AngⅡ/TGF-β1 /Smads is an important mechanism, while atrial fibrosis is the core pathological change of HFpEF. Our previous research found that, on the basis of the successful establishment of HFpEF animal model, Linggui Qihua Fang can significantly improve the diastolic function and atrial fibrosis of HFpEF , but the mechanism was unclear. Therefore, we propose a hypothesis: AngⅡ/TGF-β1/Smads is an important signal pathway to promote the development of HFpEF and Linggui Qihua Fang can improve HFpEF by regulating it. To test this hypothesis, We will establish a composite HFPEF model with multi-risk factors, adopt advanced bioinformatics, molecular biology technology and dot ultrasound, confirm the role of AngⅡ/TGF-β1/Smads signal pathway in HFPEF from the molecular, cellular and gene levels and clarify the mechanism of Linggui Qihua Fang on HFpEF. We will reveal the mechanism of HFpEF and the mechanism of TCM on HFpEF from a new perspective, which will provide experimental basis for the prevention and treatment of TCM on HFpEF.