肾脏（前）肾素受体调控Wnt/β-Catenin信号对肾性高血压所致心肌肥厚的作用与机制

Myocardial hypertrophy caused by renal hypertension is an independent risk factor of sudden death in patients with chronic kidney disease(CKD). It does serious harm to human health, The efficacy of traditional Renin-Angiotensin System (RAS) inhibitors such as ACEI or ARB is often limited. One possible explanation is lack of simultaneous inhibition of multiple components of RAS in the kidney. As multiple components of RAS are the downstream targets of Wnt/β-Catenin signaling.Our recent studies have shown that renal (pro) renin receptor (PRR) affected the progression of CKD via Wnt/β-Catenin signaling and knockdown of renal PRR ameliorated the myocardial hypertrophy in hypertensive rats. then We hypothesize that renal PRR may affect the Wnt/β-Catenin signaling via the RAS activation in the progression of Myocardial hypertrophy inuced by renal hypertension. In vivo and in vitro,We will study the effects and mechanisms of the myocardial hypertrophy in hypertensive rats by over-expression of renal PRR and compare the therapeutic efficacy of inhibition of renal PRR with traditional RAS inhibitors in the treatment of Myocardial hypertrophy caused by renal hypertension. This study will provide a new perspective for elucidating the pathogenesis and have important clinical significance for formulating more effective treatment of Myocardial hypertrophy caused by renal hypertension.

肾性高血压导致的心肌肥厚是慢性肾脏疾病（CKD）患者猝死的独立危险因素，肾脏肾素-血管紧张素系统（RAS）激活是心肌肥厚进展的重要原因，传统ACEI、ARB等药物疗效欠佳，原因可能是不能同时抑制肾脏RAS多组分活化。由于RAS多组分是Wnt/β-Catenin通路下游靶点，我们近期研究发现：肾脏（前）肾素受体（PRR）通过调控Wnt/β-Catenin通路活性影响CKD进展，同时预实验发现敲除肾脏PRR可以抑制肾性高血压所致心肌肥厚的进展，我们设想：肾脏PRR通过Wnt/β-Catenin信号调控RAS多组分影响肾性高血压所致心肌肥厚的进展。我们将在体内、外探讨：分别过表达/抑制肾脏PRR上调/下调Wnt/β-Catenin通路对肾性高血压所致心肌肥厚的影响和机制及与传统RAS抑制剂的疗效比较。这将为进一步阐释肾性高血压导致心肌肥厚的发病机制提供新视角，亦为制定更有效的治疗策略具备重要意义

肾性高血压导致的心肌肥厚是慢性肾脏疾病（CKD）患者猝死的独立危险因素，肾脏肾素-血管紧张素系统（RAS）激活是心肌肥厚进展的重要原因，传统ACEI、ARB等药物疗效欠佳，原因可能是不能同时抑制肾脏RAS多组分活化。本项目通过肾性高血压动物模型分别过表达\抑制肾脏PRR观察CKD状态下肾脏PRR的表达量对于肾性高血压所致心肌肥厚的影响，发现CKD状态下过表达肾脏PRR通过活化肾脏RAS明显促进了肾性高血压所致心肌肥厚的进展，而抑制肾脏PRR通过全面抑制肾脏RAS对于肾性高血压所致心肌肥厚的进展的疗效明显优于传统ACEI及ARB等药物，本项目有助于阐明肾脏PRR调控Wnt/β-Catenin 信号关系在影响肾脏RAS活化在肾性高血压所致心肌肥厚的作用，为进一步揭示肾性高血压和心肌肥厚发病机制提供新视角和新的致病因子，亦为探索一种更为有效、更为新颖的治疗方法具备重要临床意义。