蜂胶黄酮及其单体对巨噬细胞内质网应激凋亡途径的调控作用及机制

项目名称： 蜂胶黄酮及其单体对巨噬细胞内质网应激凋亡途径的调控作用及机制

项目编号： No.81202949

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： 姚树桐

作者单位： 泰山医学院

项目金额： 23万元

中文摘要： 内质网应激(ERS)凋亡途径介导巨噬细胞凋亡并影响动脉粥样硬化(AS)斑块稳定性。我们既往研究和文献报道证实蜂胶黄酮及其单体槲皮素可抑制血管内皮和巨噬细胞凋亡，但其机制尚未完全阐明。来自神经和肠上皮细胞的研究表明蜂胶和槲皮素可抑制ERS诱导剂所诱导的细胞凋亡。因此我们假设蜂胶黄酮及其单体通过抑制ERS凋亡途径调控巨噬细胞凋亡，发挥其抗AS作用。本项目拟在氧化低密度脂蛋白和ERS诱导剂衣霉素诱导的巨噬源性泡沫细胞模型和ERS模型以及apoE-/-小鼠AS模型上，采用免疫印迹、免疫组化、实时定量PCR等方法，研究蜂胶黄酮及其单体槲皮素和乔松素对C/EBP同源蛋白(CHOP)、c-Jun氨基末端激酶(JNK)、caspase-12等ERS凋亡途径相关分子表达和活性的影响及其与巨噬细胞凋亡之间的关系，以进一步阐明蜂胶及其有效成分抗AS作用机制，并为黄酮类化合物药理作用机制研究提供新思路。

中文关键词： 动脉粥样硬化；内质网应激；巨噬细胞；血管内皮细胞；蜂胶黄酮类化合物

英文摘要： Endoplasmic reticulum stress (ERS)-mediated apoptosis in macrophages has been demonstrated to contribute to the instability of atherosclerotic plaques. We and other groups have found that propolis flavonoids and quercetin, a monomer of ?avonoids in propolis, protect macrophages and vascular endothelial cells from apoptosis stimuli, but the underlying mechanisms are not elucidated clearly. The studies from neuronal and intestinal epithelial cells have shown that propolis extract and quercetin inhibit apoptosis induced by ERS inducers. Therefore, we assume that propolis flavonoids and its monomers may regulate macrophage apoptosis and play an anti-atherosclerotic role through suppressing ERS-mediated apoptosis pathway. This study is designed to investigate the effects of propolis ?avonoids and its monomers, such as quercetin and pinocembrin, on the apoptosis in macrophages induced by oxidized low density lipoprotein (ox-LDL) or tunicamycin (a classical ERS inducer) and on the advanced atherosclerotic lesions of apoE-knockout mice. The ERS-mediated apoptosis pathways, which include C/EBP homologous protein (CHOP), c-Jun amino-terminal kinase (JNK) and caspase-12 pathways, are explored via Western blotting, immunohistochemistry, real-time PCR, and so on. This work will explain the diverse anti-atherosclerotic mechan

英文关键词： atherosclerosis；endoplasmic reticulum stress；macrophages；vascular endothelial cells；propolis flavone