高血压是引起心力衰竭的常见病因，其病理生理过程中的关键在于心肌重塑。研究发现MMP-9及Ⅲ型胶原的过度表达和炎性细胞浸润增强是导致心室重塑的重要原因，且NF-κB信号通路在心室重塑过程中持续激活。研究表明抑制NF-κB通路的激活能减轻小鼠心肌梗塞后的心室重塑、改善心功能。据此，本课题拟采用主动脉缩窄动物模型复制压力超负荷性心力衰竭，探讨NF-κB通路在此种类型心衰中的作用及分子机制；同时，以NF-κB信号通路为干预靶点，利用重组腺相关病毒AAV9载体介导siRNA抑制大鼠心肌细胞NF-κB p65的表达，靶向转导大鼠心肌，通过检测NF-κB活性及通路中相关蛋白、炎症因子及胶原表达、细胞凋亡、MMPs活性、心肌病理损害程度、心功能等指标，阐明靶向抑制NF-κB信号通路防治压力超负荷性心力衰竭的作用及分子机制，明确基因靶向干预治疗的有效性和可行性。

Hypertension is a common cause of heart failure, and its pathophysiological key is myocardial remodeling. The study found the excessive expression of MMP-9 and type Ⅲ collagen and enhancement of inflammatory cells infiltrating play an important role in cardiac remodeling, meanwhile NF-κB signal pathway was activated in chronic cardiac remodeling process. Previous studies have demonstrated that NF-κB activation inhibited attenuated mouse cardiac remodeling and improved heart function. So, this research explore the effects and mechanisms of NF-κB signal pathway in pressure overload animal model with aortic coarctation, meanwhile inhibit the expression of P65 by recombinant adeno-associated virus containing small interfering RNA(siRNA) targeting rat NF-κB p65 mRNA (Ad-NF-κB p65-siRNA), to investigate the index of NF-κB signal pathway activity and related protein, collagen protein and inflammatory factors expression, MMPs activity, myocardial pathological damage, infarct size and cardic function, et al. Meanwhile investigate the targeted inhibition of NF-κB signaling pathway to prevent and cure the pressure overload heart failure and molecular mechanisms, to identify gene targeting for therapeutic intervention effectiveness.