单核-巨噬细胞在"痰瘀互结"致动脉粥样硬化的作用及丹蒌片干预机制研究

项目名称： 单核-巨噬细胞在"痰瘀互结"致动脉粥样硬化的作用及丹蒌片干预机制研究

项目编号： No.81202782

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 王磊

作者单位： 广州中医药大学

项目金额： 23万元

中文摘要： 动脉粥样硬化（AS）是严重危害人类健康的重要疾病，单核-巨噬细胞在AS发生中发挥至关重要的作用，"痰瘀互结"是AS发生的重要病因病机，与炎症反应密切关系，前期研究发现，活血化痰中药丹蒌片具有良好的抗AS作用，但其确切机制尚未阐明。我们推测"痰瘀互结通过促使单核-巨噬细胞的异常分化，加速巨噬细胞泡沫化过程，导致AS的发生；丹蒌片通过抑制单核-巨噬细胞异常分化和巨噬细胞泡沫化过程，而发挥防治AS的作用"。为证实该假说，本研究以Apo-E基因敲除小鼠颈动脉损伤方法构建痰瘀互结型AS模型，通过流式细胞仪和细胞免疫组化技术，探讨单核-巨噬细胞亚型的表达规律及其作用机制，同时观察丹蒌片对AS模型中单核-巨噬细胞亚型表达的调节；构建巨噬细胞和泡沫细胞，观察观察丹蒌片对巨噬细胞炎症因子释放和泡沫化的影响及机制。本研究的开展将进一步揭示痰瘀互结致AS的发生机制，为其有效防治提供新思路和药物作用的新靶点。

中文关键词： 动脉粥样硬化；缺血再灌注损伤；巨噬细胞；炎症；痰瘀同治

英文摘要： Atherosclerosis(AS) is a serious disease hazards to humankind. Monocyte-macrophages play key roles on AS formation. Intermingled Phlegm and Blood Stasis are important etiological and pathological factors in Traditional Chinese Medicine theory, closely related with inflammation.Preliminary data showed that Dan-Lou Tablets took good performance in preventing and treating AS. However,the exact mechanisms are still unclear up to now. Our hypothesis is that Intermingled Phlegm and Blood Stasis can promote the abnormal differentiation of monocyte-macrophages and accelerate the formation of foam cells, resulting in AS.Also we hypothesize that Dan-Lou Tablets can prevent AS by regulating the abnormal differentiation of monocyte-macrophages and inhibit the formation of foam cells. The AS model of Intermingled Phlegm and Blood Stasis will be established by using ApoE -/- mice with carotid artery injury.The expressions and mechanisms of monocyte-macrophage subtypes will be systematically studied by taking flow cytometry and immunohistochemistry methods. Furthermore,we will explore the effects and mechanisms of Dan-Lou Tablets on the differentiation of monocyte-macrophages. Macrophages and foam cells will be cell-cultured, and the effects of Dan-Lou Tablets on the secretion of inflammatory factors and the macrophages fo

英文关键词： atherosclerosis；ischemia reperfusion injury；macrophages；inflammation；synchronic treating phlegm and blood stasis