以miR-1为靶向的新型分子探针构建及其对糖尿病心肌病的早期监测

项目名称： 以miR-1为靶向的新型分子探针构建及其对糖尿病心肌病的早期监测

项目编号： No.81501512

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李崇佼

作者单位： 武汉大学

项目金额： 18万元

中文摘要： 糖尿病心肌病（diabetic cardiomyopathy, DCM）是一种独立于高血压、冠状动脉粥样硬化性心脏病及其他已知心脏疾病，由糖尿病引起的一种心脏结构改变和功能障碍。早期准确诊断对DCM的预防、控制和恢复至关重要，但目前还没有一种较好且公认的用于DCM早期特异性诊断的方法。研究表明microRNA有潜力成为早期特异性诊断DCM的生物标记分子，miRNA的异常表达参与介导了DCM的发病过程。miR-1在DCM发生发展过程中过度表达，其是心脏和肌肉特异性miRNA，也是心脏含量最丰富的miRNA（40%）。本研究拟以miR-1为靶分子、构建基于肽核酸（PNA）的新型分子探针99mTc-PNA，来探测细胞及动物DCM模型中miR-1的表达变化，以期在基因水平对DCM的发生发展提供一种早期、特异、无创、实时的监测手段，并为未来指导临床DCM的早期干预及个体化治疗提供基础依据。

中文关键词： 微小RNA；肽核酸；糖尿病心肌病；反义显像；单光子发射计算机断层成像

英文摘要： Diabetic cardiomyopathy (DCM) is a kind of heart disease with changes of cardiac structure and function disorders, which is caused by diabetes and independent of hypertension, coronary atherosclerosis as well as other known heart disease. Early accurate diagnosis of DCM is essential for its prevention, control and recovery. However, there is no approved method for the early and specific diagnosis of DCM. Recently, some studies have shown that microRNA may be a promising biomarker for early and specific diagnosis of DCM. The abnormal expression of miRNA was involved in mediating the pathogenesis of DCM. MiR-1 is overexpressed during the development of DCM. MiR-1 is the cardiac-specific and muscle-specific miRNA, which is the most abundant miRNA and accounted for approximately 40% of the total miRNA in heart. In this study, a novel molecular probe 99mTc-PNA targeting miR-1 will be prepared by labeling peptide nucleic acid with radionuclide 99mTc, for detecting abnormal expression of miR-1 through series of in vitro and in vivo experiments. The aim of this study is to develop a non-invasive and real-time monitoring tool for early and specific diagnosis of DCM at the genetic level, and provide the basis for future clinical intervention and individual treatment of DCM patients.

英文关键词： microRNA;peptide nucleic acid;diabetic cardiomyopathy;antisense imaging;single photon emission computed tomography