心肌纤维化是各种心肌损伤和心衰的共同通路，也是发生室性心律失常的基质。临床和基础研究发现肾去交感神经术（RDN）可抑制心房心室重构和减少心律失常发生，但机制不清楚。课题组前期研究发现RDN明显降低TAC大鼠心房、心室及肾脏的纤维化程度，由此，我们推测RDN可通过抑制TGF-β1/Smads信号通路降低心肌纤维化程度，抑制心脏重构，减少室性心律失常发生。本研究在已成功建立TAC心肌病小鼠模型基础上，检测TGF-β1/Smads信号通路及相关致纤维化因子表达水平；进一步通过阻断TGF-β1及敲除Smad2、Smad3基因，分析RDN是否通过TGF-β1/Smads信号通路减少心肌纤维化；同时利用植入子、电生理程序刺激、分子生物学及膜片钳等技术，从分子、基因、器官和整体水平探讨RDN减少TAC小鼠心肌纤维化、抑制心脏重构和室性心律失常。为RDN治疗心力衰竭提供理论基础。

Cardiac fibrosis is a common pathway for various myocardial injuries as well as heart failure (HF). Simultaneously, fibrosis of myocardium forms the substrate for ventricular arrhythmia. Previous clinical and experimental studies demonstrated that renal denervation (RDN) could inhibit atrial and ventricular remodeling, and reduce the risk of arrhythmia. The underlying mechanisms, however, remain unclear. Our previous study has shown that RDN can significantly reduce atrial, ventricular and renal fibrosis in rats underwent transverse aortic onstriction (TAC). We also observed a decreasing expression of TGF-β1 in myocardium following RDN. Hence, we assume that the ability of RDN inhibiting TGF-β1 / Smads signal pathway is responsible for the improvements of myocardial fibrosis, cardiac remodeling and ventricular arrhythmia. In a well-established mouse model of TAC-induced cardiomyopathy, we will detect the expression levels of TGF-β1 / Smads pathway components and related fibrogenic factors. In order to further determine whether the effects of RDN on cardiac fibrosis is related to TGF-β1/Smads pathway, we will adopt TGF-β1 inhibitors and Smad2/Smad3 knock-out mice. Meanwhile, Data Sciences International (DSI), electrophysiological programmed stimulation, molecular biology and patch-clamp techniques will be used, with aims to explore.the underlying mechanisms of RDN improving myocardial fibrosis, heart remodeling and ventricular arrhythmia, at molecular, genetic, organic and intact level.