心肌β１肾上腺素受体表达异质性及其影响血压的机制研究

项目名称： 心肌β１肾上腺素受体表达异质性及其影响血压的机制研究

项目编号： No.81470535

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 袁洪

作者单位： 中南大学

项目金额： 73万元

中文摘要： 目前关于高血压病的发生发展机制尚不十分清晰,探讨以相关分子分型促进诊断及治疗的评价是当前高血压研究所关注的热点之一。前期研究我们发现心肌β1-AR表达量及甲基化状态是影响美托洛尔降压疗效的重要因素之一。因此我们提出心肌β1-AR表达差异能否作为高血压不同个体间分子分型的新靶点这一假说。本项目拟开展心肌β1-AR表达异质性与血压的关系研究；建立心肌特异性β1-AR基因敲除的自发性高血压大鼠（SHR）模型，探索β1-AR表达异质性影响血压的机制；评价miR-30对心肌β1-AR的表达调控，探讨心肌β1-AR表达异质性的相关因素。从而阐明心肌β1-AR表达异质性对血压的影响及机制，为高血压诊断和治疗的分子分型提供新的思路和实验依据。

中文关键词： β1；肾上腺素受体；表达异质性；血压；分子机制

英文摘要： Currently, the mechanisms of the incidence and development of hypertension is not yet clear, and it is one of the research hotspots to explore the evaluations of relevant molecular typings for facilitating the diagnosis and treatment of hypertension. Our previous study found that the cardiac β1-AR expression and the methylation status were important factors affecting the antihypertensive efficacy of metoprolol. Therefore, we propose a hypothesis that different levels of myocardial β1-AR expression in individuals of hypertension may act as a new target for molecular typing. This project intends to study the relationship between the myocardial β1-AR expression heterogeneity and blood pressure; to establish cardiac-specific β1-AR gene knockout model in spontaneously hypertensive rats (SHR) to explore the mechanisms of β1-AR expression heterogeneity affecting blood pressure; and to evaluate the regulation of miR-30 in myocardial β1-AR expression to explore the related factors in myocardial β1-AR expression heterogeneity. These studies will clarify the effects and mechanisms of cardiac β1-AR expression heterogeneity on blood pressure,providing new ideas and experimental evidence for the molecular typing in diagnosis and treatment of hypertension.

英文关键词： β1-adrenergic receptor;expression heterogeneity;blood pressure;molecular mechanism