基于ANXA5-凋亡路径的超声微泡定向释放沉默ANXA5基因对高血压心肌重构的防治作用及机制

高血压心肌重构可导致心肌肥厚和心衰，探索心肌重构的发病机制及治疗靶点成为焦点。课题组前期研究发现膜联蛋白A5（ANXA5）基因表达可导致高血压心肌肥厚，机制与ANXA5诱导心肌细胞凋亡有关。ANXA5是抑制高血压心肌重构基因治疗的关键靶点。超声靶向微泡破坏（UTMD）因可靶向释放基因、细胞转染率高成为有效的基因释放手段。本课题采用基因芯片、RNAi技术构建沉默ANXA5表达的siRNA后转载入超声脂质微泡，UTMD心肌定向释放，从动物实验、离体心脏及细胞实验不同角度探索UTMD心肌靶向释放ANXA5沉默基因对高血压、醛固酮损伤心肌的保护作用，以及这一保护作用中凋亡相关因子在心肌细胞中表达的变化。阐明通过UTMD基因靶向治疗沉默ANXA5基因对高血压心肌的保护作用，以及ANXA5基因沉默通过调控心肌细胞凋亡通路保护高血压心肌细胞的机制，为临床治疗高血压心衰奠定理论基础和提供新的手段和策略。

Mocardial remodeling is nearly parallel in essential hypertension and lead to left ventricular hypertrophy(LVH) and hear failure(HF).Comprehending the laws of Myocardial remodeling in EH and learning the therapeutic target of it remains a major cause for concern.The are reviewed the ANXA5 gence to be associated with LVH,and the one of the reasons about it is that the ANXA5 protein introduce the apoptosis of myocardial cells.So ANXA5 is a key target for gene therapy to control Myocardial modeling.Ultrasound-targeted microbubble destruction(UTMD) is an effective gene therapy for the advantage of targeted release and high gene transfection rate.My research team build the ANXA5 siRNA to silence ANXA5 gene by gene chip and RNAi technology.The siRNA genes were loaded into lipid microbubble and release to the myocardium by UTMD.By animal experimentation,in vitro heart experiment and cell experiment, my group explore the efficacy of released ANX5 siRNA lipid microbubble in myocardial cell by UMTD and protecting EH and Aldosterone(ALD)-induced cardiomyocytes.Apoptotic factors in experimental myocardial cells were measured.In order to elucidate the pathogenesis of ANXA5 gene silencing on myocardial apoptosis and myocardial protection by UTMD gene targeting therapy.This has the capacity to provide a theoretical basis for novel treatment options for the clinical treatment of LVH and HF with EH.