如何逆转高血压心肌肥厚，延缓心肌肥厚向心力衰竭进展是目前的研究热点。既往研究报道PKC通路在压力超负荷心肌肥厚中作用存在不明之处。我们前期研究发现压力超负荷诱导心肌PKCα/β1亚型激活、JNK1/2磷酸化增加，伴随心肌细胞自噬增强；而抑制PKCβ1活性则显著下调心肌细胞自噬，动物实验也提示抑制心肌细胞自噬显著降低心肌肥厚，提示PKCβ1介导心肌肥厚进展中细胞自噬的病理过程。我们假设压力超负荷诱导产生的机械牵张效应激活心肌PKCβ1及下游JNK1/2-c-Jun通路，正向调节心肌细胞自噬，促进心肌肥厚进展；阻断PKCβ1信号可能阻止其病理过程，延缓逆转心肌肥厚。课题组拟建立小鼠TAC高血压模型、心肌细胞机械牵张模型，从动物、细胞、分子三个层面阐述PKCβ1-JNK1/2-c-Jun轴能否调控压力超负荷诱导的心肌细胞自噬，延缓逆转心肌肥厚，为临床应用PKCβ1抑制剂干预高血压心脏病提供依据。

Reversion of cardiac hypertrophy in hypertension and attenuation of the subsequent heart failure draw great attention by scientific researchers currently. Recent studies have revealed controversies over the roles of protein kinase C (PKC) signaling pathway in the development of cardiac hypertrophy. Our previous studies have found increased cardiac autophagy, the activation of PKCα/β1 and the phosphorylation of JNK in the pressure overload induced cardiac hypertrophy. We have also found the inhibition of PKCβ1 will lead to the significantly down-regulation of pressure overload induced cardiac autophagy, and the inhibition of cardiomyocyte autophagy significantly ameliorate myocardial hypertrophy in the animal experiment. This results indicate that PKCβ1 mediated autophagy plays an important role in the pressure overload induced cardiac hypertrophy. Accordingly, we hypothesize that PKCβ1-JNK signaling pathway positively regulates cardiac autophagy facilitating the pathophysiological progression of cardiac hypertrophy induced by pressure overload ; blocking PKCβ1 isoform could attenuate or even reverse the pressure overload induced cardiac hypertrophy. This study aims to establish TAC induced hypertensive mouse model, myocardial mechanical stretching model, and to investigate the role of PKCβ1-JNK1/2-c-Jun signaling pathway in the pressure overload induced cardiac autophagy in the development of cardiac hypertrophy based on knockout mice, cellular and molecular experiments, providing theoretical evidence for the application of PKCβ1 inhibitor in the clinical treatment of hypertensive heart disease.