氧化应激多模分子成像早期评价糖尿病心肌微循环损伤

氧化应激反应被认为是糖尿病心肌病最重要的发病机制，常导致心肌微循环损伤、细胞凋亡和心肌纤维化等主要病理改变。糖尿病心肌损伤临床干预困难，远期预后差。因此，糖尿病心肌损伤的早期诊断和积极干预逐渐受到重视，但目前尚缺乏针对心肌氧化应激状态和微循环损伤的早期、敏感、无创监测手段。综合文献报道及前期研究基础，课题组拟构建针对活性氧（ROS）的靶向特异性成像分子探针，结合磁共振灌注成像、功能成像及T1-mapping成像等研发多模MRI分子成像新技术以早期、敏感评价糖尿病心肌氧化应激状态、微循环损伤、心肌纤维化等影像特征；对照组织病理及生化指标进一步探明ROS导致的心肌细胞凋亡、微循环损伤及心肌纤维化在心室重构方面是否发挥协同作用，并阐释相关机制。相关研究成果可望为早期监测糖尿病心肌微循环损伤、积极探索干预措施及动态评价治疗效果提供新方法，为临床治疗决策提供科学依据。

Oxidative stress is considered to be the most important pathogenesis of diabetic cardiomyopathy (DCM), leading to microcirculation injury, myocyte apoptosis and myocardial fibrosis. Clinically, the long-term prognosis of diabetic cardiomyopathy is poor due to the management difficulties, so the early detection and intervention are gradually regarded as a new research focus of attention. However, the sensitive and non-invasive methods for early detection myocardial oxidative stress and microcirculation injury in vivo is still lacking. Based on our research achievements and previous studies, the aim of our study was to characterize the features of reactive oxygen species (ROS) for the development of target-specific molecular magnetic resonance imaging (MRI) probe. Combined with cardiac perfusion imaging, T1-mapping and functional analysis on MRI, we will explore a new strategy for early detecting myocardial oxidative stress, microcirculation injury, myocardial fibrosis and ventricular remodeling with multimodal MRI molecular imaging. When compared with the histopathological and biochemical markers, the research proposal will explore whether cardiomyocyte apoptosis, microcirculation dysfunction, myocardial fibrosis can synergistically lead to ventricular remodeling and further establish new methods for investigating DCM myocardial injury mechanisms. More importantly, our study may be potential to establish methodological strategies for early detection and intervention of diabetic cardiomyopathy, dynamically assessing therapeutic efficacy, and providing scientific evidences for clinical decision-making.