钙敏感受体（CaSR）影响颈动脉粥样硬化斑块稳定性机制的初步研究

Unstable plaque is one of the most important factors for cerebrovascular disease. Macrophages affect the stability of plaque by foaming and mediating immune inflammatory reaction. Calcium sensing receptor (CaSR) is a G protein coupled receptor, which is mainly involved in body regulation and control of Ca2+,cell secretion and activation of ion channels. Previous studies have found that CaSR is expressed in macrophages. Therefore, we speculate that CaSR may accelerate the process of macrophage foam through some cascade reaction, and at the same time promote the release of cytokines to influence the stability of atherosclerotic plaque. The subject aims to investigate the changes in the expression of CaSR in macrophages, and observe the relationship between the expression of calcium sensing receptor and the instability of plaque in different types of carotid plaques by establishing the model of atherosclerotic plaques in rats,Then explore the relationship between CaSR and plaque stability in terms of macrophage foam and cytokine secretion so as to reveal mechanism, theoretical significance and application value. The implementation of the subject is expected to provide a new idea and a new drug target for the prevention and treatment of carotid atherosclerotic plaque.

不稳定斑块是导致脑血管病事件的重要原因,巨噬细胞通过泡沫化及介导免疫炎症反应影响斑块稳定性。研究表明参与体内 Ca2+ 稳态调控及细胞因子分泌的钙敏感受体（CaSR）在巨噬细胞存在功能表达，但它与斑块稳定性之间的关联尚未可知。我们初步研究发现CaSR调控巨噬细胞IL-1β的分泌，推测其可能通过影响巨噬细胞的功能从而影响动脉粥样硬化斑块的稳定性。本课题以巨噬细胞钙敏感受体表达的变化为切入点，通过建立动脉粥样硬化斑块大鼠模型，观察不同性质颈动脉斑块内巨噬细胞钙敏感受体表达差异；并从巨噬细胞泡沫化和细胞因子分泌的角度，深入探讨CaSR与斑块稳定性的关系及其信号传导途径，从而阐明其作用机制，具有重要的理论意义和应用价值。本项目的实施可望为颈动脉粥样硬化斑块的防治提供一种新思路和药物作用新靶点。

不稳定斑块是导致脑血管病事件的重要原因，斑块形成过程中巨噬细胞通过泡沫化并介导免疫炎症反应影响斑块稳定性。表达于巨噬细胞的钙敏感受体（CaSR）参与体内钙离子稳态的调控，并可调控巨噬细胞Il -1β分泌，为探索在动脉粥样硬化斑块形成过程中钙敏感受体对于斑块稳定性的影响，本研究建立了动脉粥样硬化斑块大鼠模型，并通过超声影像学方法对模型进行评估与鉴定，证实造模组管腔内膜增厚，连续性中断，局部内膜增厚，斑块形成。在此基础上，通过实时荧光定量聚合酶链反应扩增的方法明确了钙敏感受体在斑块组与对照组的差异化表达，并通过对比巨噬细胞及其炎症趋化因子受体2（CCR2）以及肿瘤坏死因子（TNFα）的差异化表达，证实了巨噬细胞钙敏感受体在不稳定斑块形成中的作用，为进一步通过干预该受体的激活状态以预防动脉粥样硬化斑块的形成提供了新的靶点。