高血压合并糖尿病早期造成心脏损伤,出现心肌纤维化，目前机制尚不十分清楚，治疗无特异性。研究已证实前肾素受体（PRR）与心血管疾病病理过程相关。我们前期研究发现高血压合并糖尿病大鼠中，PRR基因过表达激活了YAP，有研究认为Hippo-YAP通路与心肌损伤后心肌纤维化的病理过程有关。我们提出假说：PRR通过Hippo-YAP通路促进高血压合并糖尿病心肌损伤后心肌纤维化的病理过程；本研究通过构建PRR基因过表达鼠、PRR基因条件性敲除鼠，并进行体外细胞实验，论述PRR-Hippo-YAP通路在心肌纤维化中的作用，探讨PRR激活YAP的机制，进一步探讨PRR通过YAP激活结缔组织生长因子（CTGF）基因表达及促进心肌纤维化的分子机制，目的在于阐明PRR-Hippo-YAP通路在心肌损伤后心肌纤维化中的作用及意义，为高血压合并糖尿病心肌损伤后心肌纤维化治疗提供新靶点。

Recent study showed that hypertension with diabetes may induce more serious and earlier myocardial injury than single disease. The (pro)renin receptor (PRR) is considered as a novel bioactive molecule of the renin-angiotensin system (RAS) ,and it plays an important role in hypertension, diabetes and their complications. Previous study showed that high glucose up-regulated PRR protein expression, and our study found that PRR overexpression activated Hippo-YAP pathway in rat, which had a key role in the pathogenesis of fibrosis. These studies indicated that PRR-Hippo-YAP pathway may play crucial role in the pathogenesis of myocardial injury. In this study, we test the hypothesis that PRR may promote myocardial fibrosis by activation of YAP. The PRR knock-in and PRR conditional knock-out mice were generated to evaluate the effects of PRR-Hippo-YAP pathway on the myocardial fibrosis in mice with hypertension with diabetes. In Vitro study, cardiac fibroblast culture from PRR knock-in and PRR conditional knock-out mice was performed to assess the effects of PRR-Hippo-YAP pathway on the production of collagen protein expression, and the molecular of connective tissue growth factors (CTGF) gene expression may be regulated by PRR-Hippo-YAP pathway were evaluated. This study wants to explore the effect and mechanism of PRR-Hippo-YAP pathway on myocardial injury and fibrosis, and provide new target for treatment of myocardial injury in hypertension with diabetes.