柿子单宁调节NOX2/NOX4介导泡沫细胞形成的机制研究

项目名称： 柿子单宁调节NOX2/NOX4介导泡沫细胞形成的机制研究

项目编号： No.31201351

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 膳食与营养

项目作者： 刘亮

作者单位： 武汉轻工大学

项目金额： 24万元

中文摘要： 受体介导Ox-LDL摄取后引起的巨噬细胞泡沫化是动脉粥样硬化的重要病理学标志。NADPH-oxdiase(NOXs)对巨噬细胞介导的LDL氧化具有关键作用，而NOXs介导的细胞内LDL氧化可能更为重要，但其介导效应和病理学意义至今仍被忽视。清除NOXs产生的ROS，同时抑制NOXs表达对防止LDL氧化和泡沫细胞形成意义重大。据此我们假设：柿子单宁能通过信号通路调节NOXs表达，进而减少LDL氧化和泡沫细胞形成，发挥其对血管病变的保护作用。根据假设，本研究拟采用apoE基因敲除小鼠，以资源丰富的柿子为原料，借助基因转染和RNA干扰技术，研究抗氧化功效成分柿子单宁对NOXs表达的调节机制以及NOXs对细胞内LDL和泡沫细胞形成的介导效应。本项目的实施，不仅能明确柿子单宁调节NOXs表达及泡沫细胞形成机制和NOXs介导细胞内LDL氧化机制，还对柿子综合利用和解决柿子产业开发难题具有重要指导意。

中文关键词： 柿子单宁；动脉粥样硬化；NADPH氧化酶；泡沫细胞；自噬-溶酶体

英文摘要： The formation of macrophage foam cell via receptor mediated Ox-LDL uptake is the most important pathology hallmark of atherosclerosis. Although, NADPH-oxidase has pivotal role on macrophage-mediated oxidation of LDL, NADPH-oxidase-mediated intracellular LDL oxidation may be more important. However, pathological significance of intracellular LDL oxidation for foam cell formation and mediated effect of NADPH-oxidase have remained virtually ignored. Scavenging NADPH-oxidase-derived reactive oxygen species and inhibiting NADPH-oxidase expression are of great importance for preventing LDL oxidation and foam cell formation. On these grounds, we hypothesized that persimmon tannin can regulate the expression of NADPH-oxidase through the signal pathway, thereby reduces LDL oxidation and foam cell formation, thus plays protective role on arterial injury. Under this assumption, apoE knockout mice and persimmon tannin which is major antioxidant effect component from persimmon will be used. With RNA interference and gene transfer techniques, regulatory mechanism of persimmon tannin on NADPH-oxidase expression and mediated effect of NADPH-oxidase on intracellular LDL oxidation and foam cell formation will be studied. Implementation of this research can not only confirm the regulatory mechanisms of persimmon tannin on NADPH-

英文关键词： Persimmon Tannin；Atherosclerosis;；NADPH oxidase；Foam cell；Autophagy-Lysosome