心脏成纤维细胞激活并分化为肌成纤维细胞在心衰心肌纤维化中发挥着重要作用。MLK3可能在心衰心肌纤维化中发挥着重要作用，并成为心衰治疗新的重要小分子靶标。近年来自噬在心衰心肌纤维化中的作用受到重视，MLK3/JNK-自噬机制介导的心脏成纤维细胞激活可能在心衰心肌纤维化中发挥着重要作用，调节MLK3/JNK-自噬机制介导的成纤维细胞激活可能具有改善心衰心肌纤维化的作用。益气养阴活血法作为中医心衰治疗的主要方法，可能具有调节MLK3/JNK-自噬机制防治心衰心肌纤维化的作用。本研究拟通过制备整体动物模型、培养原代细胞，利用Western blot、腺病毒载体转染、siRNA、荧光探针、qPCR、免疫荧光等方法，在细胞和整体水平研究MLK3/JNK-自噬介导的心脏成纤维细胞激活在心衰心肌纤维化的作用及机制，以及益气养阴活血法调节MLK3/JNK-自噬抑制心脏成纤维细胞激活防治心衰心肌纤维化的作用。

The activation of cardiac fibroblast plays an important roles in heart failure and cardiac fibrosis. MLK3/JNK may be a new small important molecule target. Because a lot of attention has been paid to the role of autophagy in heart failure and myocardial remodeling ,some attention has been focused on the role of the cardiac fibroblast autoghagy mediated by MLK3/JNK in heart failure and cardiac fibrosis.The regulation on cardiac fibroblast autoghagy mediated by MLK3/JNK may be a novel therapeutic strategies for heart failure and cardiac fibrosis. In the project, we will explore the role of the autophagy mediated by MLK3/JNK in cardiac fibroblast in heart failure and cardiac fibrosis in vivo and in vitro, and the effect on autophagy mediated by MLK3/JNK in cardiac fibroblast of benefiting qi, nourishing yin and activating blood in heart failure and cardiac fibrosis in vivo and in vitro. The result of research project will provide the novel theoretical basis and experimental evidence for the role of MLK3 in the heart failure and cardiac fibrosis, and the therapy of cardiac fibrosis through autophagy and by benefiting qi and nourishing yin and activating blood.