MR管壁微成像及巨噬细胞靶向技术研究G2A在动脉粥样硬化演进中的作用

G2A is a stress-induced G protein-coupled receptor. Recent studies have found that G2A is highly expressed on the surface of macrophages in atherosclerotic plaques. However, the effect of G2A on macrophages has the function of pro-atherosclerosis and anti-atherosclerosis. We infer that the role of G2A-mediated macrophages may be different during different stages of atherosclerosis. In this study, we aimed to investigate the effect of G2A on macrophages. Based on the LDLR-/- mice, microstructure MR imaging and targeting of a specific macrophage subpopulation were used to dynamically monitor and study the effects of G2A on macrophage apoptosis, phenotypic changes within carotid atherosclerotic lesions. based which an accurate and reliable MR protocol and data analysis method will be further built for the assessment the role of G2A in AS. So this study will reveal the different effects of G2A on macrophages during the development of AS in a comprehensive and direct way, providing new ideas for the treatment of different stages of AS.

G2A是应激诱导的G蛋白偶联受体。近期研究发现G2A高表达于动脉粥样硬化（Atherosclerosis，AS）斑块内的巨噬细胞表面，但G2A对巨噬细胞的作用，既有促AS功能，也有抑AS功能。我们假设在AS的不同发展阶段，G2A所介导的巨噬细胞的作用可能不同。本项目以G2A对巨噬细胞的作用为切入点，以LDLR-/-小鼠为研究基础，运用MR管壁微观成像和巨噬细胞靶向技术动态监测和研究：AS演进过程中，G2A对巨噬细胞数量、表型变化的作用，进而建立可靠评估G2A作用的MR微观靶向技术及解析方法。本研究将较全面直观地揭示G2A在AS发展不同阶段对巨噬细胞的不同作用，从而为AS不同发展阶段的干预提供新思路。

本课题在多重因素介导的动脉粥样硬化易损斑块动物模型中，在7.0T MR成像平台上，完成了高分辨率多对比序列的参数优化，基本实现了评估动物模型（小鼠）动脉粥样硬化特征的高质量图像要求。通过与病理对照证实了7.0T MR检测小鼠颈动脉粥样硬化斑块主要特征的可靠性，建立动态监测动脉粥样硬化斑块形态、组织学特征的成像方法并进行了影像-病理验证，优化和建立了分析斑块易损性和透壁炎症的MR-VWI药代动力学；揭示了巨噬细胞、新生血管与斑块易损性之间的时空关联性，为动脉管壁和外膜炎症的诊断和风险性评估提供新的手段。另外通过临床对照研究，发现糖尿病及其血生化（高水平HbA1c）对促进动脉粥样斑块易损性和透壁炎症密切相关；进一步通过临床对照研究对颅内外大血管动脉粥样斑块炎症在急性初发及再发脑梗中的作用进行了验证。揭示了管壁MR Gd-DTPA增强技术可以评价斑块内及外膜炎症程度，在临床特别是在急性脑梗患者中的责任颈动脉或颅内斑块的炎症程度的评估中的运用及脑梗的二级预防有很重要作用。