心肌重构是心衰发生的结构基础。我们前期的研究证实蛋白激酶D（PKD）通过调控下游肌细胞增强因子2D（MEF2D），参与高血压心肌重构。高血压时出现心脏能量代谢重构，心肌细胞主要能量来源由游离脂肪酸转变为葡萄糖氧化，且代谢底物转变早于心肌重构的发生及心功能受损。葡萄糖转运蛋白4（Glut4）是介导心肌细胞葡萄糖摄取的主要载体。最近的研究提示PKD参与介导心脏收缩引起的Glut4转位以及葡萄糖的摄取。本课题综合国内外研究现状和前期研究结果，拟以自发性高血压大鼠（SHR）以及肥大细胞为模型，分别在体内体外实验中，借助于激动剂、抑制剂及基因敲除技术，分别过表达及沉默PKD和MEF2D，研究PKD/MEF2D/Glut4信号通路介导的心脏糖代谢异常参与调控心肌重构的过程。本课题研究成果将对PKD参与心肌重构的分子机制的阐明及高血压并发症的防治提供一种新的理论依据和治疗策略。

Myocardial remodeling is the structural basis of heart failure. Our previous studies confirmed that protein kinase D (PKD) is involved in hypertensive myocardial remodeling by regulating downstream myocyte enhancer 2D (MEF2D). Cardiac energy metabolism remodeling occurs in hypertension. The main energy source of myocardial cells changes from free fatty acid (FFA) to glucose oxidation, and the metabolic substrates change earlier than the occurrence of myocardial remodeling and impaired cardiac function. Glucose transporter 4 (Glut4) is the main carrier of glucose uptake in cardiomyocytes. Recent studies suggest that PKD is involved in Glut 4 translocation and glucose uptake induced by cardiac contraction. In this study, we will take spontaneously hypertensive rats (SHR) and mast cells as models to study the role of abnormal cardiac glycometabolism mediated by PKD/MEF2D/Glut4 signaling pathway in regulating myocardial remodeling by over-expression and silencing of PKD and MEF2D in vivo and in vitro, respectively, with the help of agonists, inhibitors and gene knockout techniques. The results of this study will provide a new theoretical basis and therapeutic strategy for the elucidation of the molecular mechanism of PKD in myocardial remodeling and the prevention and treatment of hypertension complications.