精氨酸酶抑制剂改善2型糖尿病心肌微循环障碍的机制及非增强负荷T1 mapping成像研究

2型糖尿病（T2DM）易发心衰和心血管事件。文献证实T2DM疾病早期即存在心肌微循环障碍（MVD），降糖治疗无法完全阻止MVD进程。有文献显示精氨酸酶（Arg）抑制剂可通过提高内皮细胞一氧化氮（NO）含量改善内皮功能，从而缓解T2DM肢体MVD，但是能否改善心肌MVD及其机制目前还不清楚。磁共振非增强负荷T1 mapping有望通过检测心肌T1值随血液灌注的变化，在无需钆对比剂情况下定量评估心肌微循环。本研究拟构建T2DM兔模型，在此模型上验证非增强负荷T1 mapping的技术可行性；通过与心肌首过灌注技术的比较，探讨该技术的优势；通过Arg抑制剂进行干预，研究心肌内皮的Arg I表达和活性、活性氧簇（ROS）和NO含量等分子生物学及磁共振成像上的改变情况，探讨Arg抑制剂改善MVD的机制及影像学表现。从而为T2DM心肌MVD的影像诊断、疗效评估及Arg抑制剂的治疗机制提供新的依据。

Type 2 diabetes mellitus (T2DM) is prone to heart failure and cardiovascular events. Previous studies showed that microcirculation disorder (MVD) exists in the early stage of T2DM, and hypoglycemic therapy can not completely prevent the procession of MVD. It has been reported that arginase inhibitors can improve endothelial function by increasing nitric oxide (NO) content in endothelial cells, thereby alleviating limb MVD in T2DM. However, whether arginase inhibitors can improve myocardial MVD and its mechanism are still unclear. Non-contrast stress T1 Mapping is expected to quantitatively evaluate myocardial microcirculation without gadolinium contrast agent by detecting the changes of myocardial T1 value. In this study, we intend to validate the technical feasibility of non-contrast stress T1 Mapping using T2DM rabbits; to explore the advantages of this technique by comparing with first-pass perfusion technique; to explore the mechanism and imaging manifestations of arginase inhibitors relieving MVD by studying the myocardial changes in molecular biology, including arginase I expression and activity, reactive oxygen species (ROS) and NO content, and in magnetic resonance imaging in myocardium by intervening with arginase inhibitors. This study will provide a new basis for imaging diagnosis, therapeutic evaluation of myocardial MVD and therapeutic mechanism of arginase inhibitors in T2DM.