中文摘要
我们发现,药理性纠正小鼠斑块微环境稳态失衡可减少炎症依赖性动脉斑块形成。选择参与炎症细胞滚动、粘附的血管粘附蛋白-1、被斑块炎症反应激活的巨噬细胞表面外周型苯二氮卓受体、使斑块坏死核心增大的凋亡巨噬细胞、使斑块纤维帽变薄的凋亡平滑肌细胞等能够反映动粥斑块演化进程的重要微环境靶标,自主构建相应分子探针68Ga-DOTAVAP-P1,18F-FEDAA1106,68Ga-NOTA-Duramycin,99mTc-SytI-C2A, 采用多模态分子显像技术在高脂诱导ApoE-/-小鼠动粥模型上构建斑块微环境靶标定量可视化方法。此成果不仅能解决当前缺乏活体动态定量方法观察斑块炎症微环境靶标的技术瓶颈问题,还可以实现使小分子靶向药物改善斑块微环境药效评价技术进入到“活体无创、动态实时、定量可视”体内分子研究水平,为评价具有我国自主知识产权的靶向血管稳态新药体内精确击靶作用提供支持,属技术领域创新。
英文摘要
Our previous study suggested that the improvements were found in the reduction on inflammation-dependent foramation of arterial plaques in mice were by pharmacological ameliorateing inflammatory microenvironment disbalance.. In this investigation,these important molecular targets,such as vascular adhesion protein - 1, which participates in the transfer of scroll, adhesion and inflammatory cells,macrophages surface peripheral benzodiazepine receptors activated by inflammatory response, the apoptotic macrophages, making the plaque necrotic core increase,the apoptotic vascular smooth muscle cells to be susceptible for thin unstable fibrous cap in the plaques,were studied based on the four novel imaging probes,such as 68Ga-DOTAVAP-P1,18F-FEDAA1106,68Ga-NOTA-Duramycin,99mTc-SytI-C2A. . The purpose of the study focuses on building up a new method of quatitative insualization for the molecular targets in plaque inflammatory microenvironment,based on atherosclerosis model in ApoE -/- mice induced by high fat diet . . This novel technique will not only be used for dynamic observations on the plaques environmental targets in atherosclerotic mice,but also for evaluation and investigation on the beneficial effect of a new AMPK agonist IMM-H007 with patents on arterial plaque stability in mice and its mechanisms.. Not only can the study solve the current bottleneck problems lacking of living dynamic observation of quantitative visualization artery plaque inflammation microenvironmental targets and new drug evaluation technology, and also can make the trational pharmacological methods get into the "living noninvasive, dynamic real-time, quantitative visualization" molecular research level in vivo, which support technical help for the evaluation on exact targeting vascular homeostasis new drugs with China patents in vivo. It belongs to the technical system innovation.
