MicroRNA在右心衰竭发展过程中的动态表达和功能鉴定

Right ventricule dysfunction is a major independent predictor of death resulting from cardiac and/or pulmonary vascular disease. The studies of mechanism in right heart failure at home and abroad are still in its infancy and the current treatment of right heart failure almost is all traditional and empirical. In this study, we will screen right ventricular myocardial miRNA expression profiles in the right ventricular hypertrophy and failure model in rat caused by monocrotaline and pulmonary artery ligation (PAB) respectively by microarray analysis, and compare the differences in miRNA expression in the left and right ventricular pressure overload cardiac hypertrophy, in order to identify the unique miRNA changes in right ventricular remodeling. Then we'll analyze the dynamic changes in right ventricular myocardial microRNA profiles in a longitudinal and crossover design during the development of ventricular remodeling, identify the tagert genes of microRNAs we screened and discover the relationship between myocardial apoptosis and extracellular matrix in the change. Through the above study, we can clarify the role of miRNAs in pressure overload right ventricular hypertrophy and failure, myocardial remodeling process and related mechanisms for a new target for further study of the therapeutic intervention of right ventricular hypertrophy and right heart failure.

右心功能是许多心脏疾病和肺血管疾病患者死亡的主要独立预测因子之一，而右心衰竭的机制研究在国内外均处于起步阶段。本研究首先利用miRNA芯片技术，分别在野百合碱（MCT）大鼠肺动脉高压右室肥厚及衰竭模型和肺动脉结扎(PAB)大鼠右室肥厚模型中分析右室心肌内miRNA差异表达谱，同时比较左右心室在压力负荷下心肌肥厚过程中miRNA表达的差异，以分析在右室重塑过程中特有的miRNA变化。然后，进一步对差异表达miRNA的靶基因在MCT肺高压大鼠模型右室肥厚重塑过程中的变化规律进行研究，分析差异表达miRNA同右室肥厚心肌重塑的整体功能参数如右心功能，心肌重塑指标，以及心肌内细胞凋亡和细胞外基质成的改变间的关系。通过以上研究，阐明miRNA在压力超负荷状态下右室肥厚及衰竭心肌重塑过程中的作用和相关机制，为进一步研究右室肥厚及右心衰竭治疗干预供新的靶点。

右心功能是许多心脏疾病和肺血管疾病患者死亡的主要独立预测因子之一，而右心衰竭的机制研究在国内外均处于起步阶段。本研究成功建立了野百合碱（MCT）大鼠肺动脉高压右室肥厚及衰竭模型和肺动脉结扎(PAB)大鼠右室肥厚模型。并使用了miRNA芯片分析了动物模型右室心肌的miRNA表达谱，并利用定量PCR技术验证，筛选出16个差异表达的miRNA。随后利用生物信息学技术预测其靶基因及其调控的功能，并在动物模型形成的不同时点对差异miRNA时序性表达变化规律分析，为以后的进一步深入研究提供重要的基础性资料，为将来的研究提供干预靶点。