研究表明心力衰竭时EndMT是心力衰竭心肌纤维化的重要病理机制。抑制EndMT被认为是防治心力衰竭心肌纤维化的新策略。但调控EndMT的机制尚不清楚，探索调控EndMT的机制将为防治心力衰竭心肌纤维化寻找到新的治疗靶点。近年来，AGEs和自噬在心力衰竭心肌纤维化的作用开始受到重视，本课题组和多项研究表明AGEs具有诱导内皮细胞自噬的作用，且自噬机制在EndMT中发挥着重要作用，因此，AGEs-自噬-EndMT机制可能在心力衰竭心肌纤维化中发挥着重要作用。益气温阳活血法是中医药防治心力衰竭的主要治法，可能具有调节AGEs-自噬-EndMT机制防治心力衰竭心肌纤维化的作用。本研究拟通过制备整体动物模型、利用转基因动物和培养血管内皮细胞，利用腺病毒载体转染、siRNA、免疫荧光等方法，在细胞和整体水平研究AGEs-自噬-EndMT机制在心力衰竭心肌纤维化的作用以及益气温阳活血法的调节作用。

EndMT play an important role in the development of heart failure and cardiac fibrosis. Inhibition of EndMT may be a novle therapeutic strategies for heart failure and cardiac fibrosis. But the upstream regulatory of EndMT remain unclear. In these years, a lot of attention has been focused on the roles of AGEs and autophagy in heart failure and cardiac fibrosis. Some studies show AGEs induce autophagy in endothelial cells. Autophagy plays an important role in EndMT. So AGEs-autophagy-EndMT have been proposed as importan mechnism involved in the development and progression of heart failure and cardiac fibrosis. Benefiting qi, warming yang and activating blood may regulate AGEs-autophagy-EndMT in heart failure and cardiac fibrosis. In the project, we will explore the roles of AGEs-autophagy-EndMT mechanism in heart failure and cardiac fibrosis in vivo and in vitro, and the effect on AGEs-autophagy-EndMT of Benefiting qi, warming yang and activating blood in heart failure and cardiac fibrosis in vivo and in vitro. The results of this project will provide the theoretical basis and experimental evidence for the role of AGEs-autophagy-EndMT in heart failure, the therapeutic role of Benefiting qi and warming yang and activating blood via regulating AGEs-autophagy-EndMT.