射血分数保留的心衰（HFpEF）时运动不耐受是其最主要的临床症状之一，与患者的预后不良及生活质量降低直接相关。骨骼肌病理性重塑是导致运动不耐受的主要机制。合理运动是改善骨骼肌重塑、提升HFpEF患者运动能力最有效的方法，但其作用机制尚未阐明。肌肉因子血管内皮生长因子B（VEGFB）在骨骼肌中高表达，具有显著的改善骨骼肌重塑的效应。本项目在我们前期工作观察到运动促进HFpEF大鼠比目鱼肌VEGFB表达的基础上，拟于在体和离体VEGFB敲除模型上，以骨骼肌毛细血管生成、线粒体氧化功能等为指标，观察VEGFB介导运动改善骨骼肌重塑；以内皮细胞增殖、迁移、线粒体呼吸功能为指标，观察VEGFB作用的靶点；以VEGFB缺失及过表达动物和细胞为模型，观察VEGFB的作用机制，以论证VEGFB是逆转HFpEF时骨骼肌重塑的内源性防御体系，探讨其细胞分子机制。

Exercise intolerance is the major clinical symptom of heart failure with preserved ejection fraction, which directly link to poor prognosis and decreased life quality. Skeletal muscle pathological remodeling is the main mechanism of exercise intolerance. Appropriate exercise is the most effective method to improve skeletal muscle remodeling and exercise capacity, but the direct material of exercise has not been clarified. Vascular endothelial growth factor-B is abundant in skeletal muscle and can improve skeletal muscle remodeling significantly. In preliminary work, we found treadmill running increased the expression of VEGFB in soleus muscle in HFpEF rats. In present project, we investigate the skeletal muscle angiogenesis and mitochondrial proliferation and oxidative function in vivo and in vitro VEGFB knockout model and test whether the effect of exercise on skeletal muscle remodeling is depended by VEGFB. In addition, we observe the endothelial cell proliferation and migration, number of mitochondria and the expression and activity of oxidase to explore the target of VEGFB. On the basis of VEGFB overexpression and knockout model, we want to elucidate the molecular mechanisms of VEGFB and demonstrate that VEGFB is an endogenous protective substance involving in exercise improved skeletal muscle remodeling in HFpEF.