基于MMP-2的MRI分子成像评价糖尿病动脉粥样硬化斑块稳定性的实验研究

项目名称： 基于MMP-2的MRI分子成像评价糖尿病动脉粥样硬化斑块稳定性的实验研究

项目编号： No.81471722

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： 杨志刚

作者单位： 四川大学

项目金额： 75万元

中文摘要： 2型糖尿病患者多器官损害中以心血管系统为最主要的靶器官。糖尿病大血管病变的主要病理过程是动脉粥样硬化。糖尿病动脉粥样斑块比非糖尿病患者发生更早、进展更快、更易破裂，因此对糖尿病动脉粥样硬化斑块稳定性的评价显得更为迫切。本研究拟构建能特异识别斑块中基质金属蛋白酶-2（MMP-2）和I型胶原纤维的MRI分子靶向探针（Ab-MMP-2-SPIO和GKWHCTTKFPHHYCLY-Gd-DOTA），通过MRI分子成像靶向显示斑块中I型胶原纤维和MMP-2成分，实现从分子水平评价糖尿病动脉粥样硬化斑块的稳定性；结合组织病理学结果，澄清糖尿病与非糖尿病动脉粥样硬化斑块稳定性的差异；力图从胶原纤维形成和破坏的角度去阐明糖尿病动脉粥样硬化易损性的机制；从而为临床早期干预糖尿病动脉粥样斑块提供科学依据。

中文关键词： 分子影像；动脉粥样硬化；2型糖尿病；磁共振成像

英文摘要： The cardiovascular system is the most prominent involved target in type 2 diabetes mellitus patients with multiple organ injury. Diabetes mellitus is associated with aggressive vascular abnormalities, and atherosclerosis is regarded as the leading cause of morbidity and mortality in diabetic patients. Atherosclerotic plaques in diabetic patients are earlier onset, faster progress,higher risk of rupture in comparison to those in non-diabetic patients. In view of these risk factors, urgent evaluation of the stability of diabetic atherosclerotic plaques are necessary. In our research proposal, we intend to synthesize a collagen-targeted MRI probe (GKWHCTTKFPHHYCLY-Gd-DOTA) for detecting plaque fibrosis with type I collagen-specific peptide. Moreover, a specific matrix metalloproteinase -2 (MMP-2) antibody probe (Ab-MMP-2-SPIO) will be synthesized chemically for detecting MMP-2 in the plaque on melecular MR images. On the basis of the molecular imaging, we will analyse and determine the stability of atherosclerosis plaque in type 2 diabetes mellitus patients. Compared histopathologic findings with molecular MR imaging, the differences of stability between diabetic and non-diabetic atherosclerotic plaques will be explored. We are hopeful that the mechanisms would be clarified in regard to the vulnerability of diabetic atherosclerotic plaques based on the formation and destruction of collagen fibers. Furthermore, the study work may be potential to provide scientific evidences for early intervention diabetic atherosclerotic plaques.

英文关键词： Molecular imaging;Atherosclerosis;Type 2 diabetes mellitus;MRI