脂蛋白循环免疫复合物致动脉粥样硬化机制的研究

发布时间：2018-05-09 11:24

本文选题：脂蛋白循环免疫复合物 + U937细胞　；参考：《南京师范大学》2006年硕士论文

【摘要】：研究背景：氧化修饰脂蛋白在动脉粥样硬化(Artherosclerosis，As)发生、发展中起着重要作用。氧化型低密度脂蛋白(Oxidatized-low density lipoprotein，Ox-LDL)免疫原性发生改变，在体内产生自身抗体并与之结合，，形成LDL循环免疫复合物(immune complex，IC)，高LDL-IC水平是As发生的预测指标。LDL-IC是一种很强的诱导物，经FcR γ受体途径诱导胆固醇酯在人单核巨噬细胞内堆积转化为泡沫细胞，且效果强于其他途径；同时释放多种细胞因子、破坏血管内皮、诱导平滑肌细胞增殖，加速As进程。高脂蛋白(a)[Lipoprotein(a)，Lp(a)]由载脂蛋白(a)[apolipoprotein(a)，apo(a)]和apoB通过二硫键连接而成，其结构、脂肪酸组成和抗氧化剂含量及体外氧化行为均与LDL相似。As斑块及人血浆中存在Ox-Lp(a)、自身抗体及其Lp(a)-IC，且冠心病患者Lp(a)-IC水平显著升高。基质金属蛋白酶(matrix metalloproteinase，MMP)及其抑制物组织金属蛋白酶抑制剂(tissue inhibitors of metalloproteinase，TIMP)降解细胞外多种基质成分，维持组织结构的完整和内环境的稳定，两者之间保持着一种动态平衡。一旦失衡，易于导致As斑块破裂，引发急性冠状动脉综合症(acute coronary syndrome，ACS)。As斑块周围多种活性细胞分泌γ干扰素，γ干扰素对As过程有多重作用，参与上述过程。有关Lp(a)-IC是否同样导致泡沫细胞形成参与As进程?对MMP、TIMP表达的影响，以及γ干扰素在其中的作用等未见报道。目的：1．探讨Lp(a)-IC对巨噬细胞转化为泡沫细胞并参与As形成的影响。2．LDL-IC、Lp(a)-IC对U937细胞MMP-1及其抑制物TIMP-1 mRNA表达的影响。3．γ干扰素对IC诱导U937细胞MMP-1表达的影响。方法：1．采用人源的氧化、天然Lp(a)及LDL与异源的抗apoB结合制备IC，观察不同浓度的Lp(a)-IC对小鼠腹腔巨噬细胞胆固醇酯的蓄积和泡沫细胞形成效果。2．采用不同浓度的LDL、Lp(a)及其IC作用于U937细胞，RT-PCR分析U937细胞中MMP-1和TIMP-1mRNA表达。3．采用不同浓度γ干扰素与LDL-IC共同作用于U937细胞，通过RT-PCR分析U937细胞中MMP-1 mRNA表达。
[Abstract]:Background: oxidative modified lipoproteins play an important role in the pathogenesis and development of atherosclerosis. The immunogenicity of Oxidatized-low density protein (Ox-LDL) is changed, and autoantibodies are produced and combined with it to form LDL circulating immune complex. High LDL-IC level is the predictor of as. LDL-IC is a strong inducer. FcR 纬 receptor pathway induces cholesterol ester accumulation and transformation into foam cells in human mononuclear macrophages, and its effect is stronger than other pathways. At the same time, many cytokines are released, vascular endothelium is destroyed, smooth muscle cells are induced to proliferate, and as process is accelerated. High lipoprotein (apoB) is composed of apolipoprotein a (apolipoprotein a) and apoB via disulfide bonds. The fatty acid composition, antioxidant content and oxidation behavior in vitro were similar to those of LDL. The presence of Ox-LpAX in plaque and human plasma, the autoantibodies and LpPPA-ICs, and the level of Lp(a)-IC in patients with coronary heart disease were significantly higher than those in patients with coronary heart disease (CHD). Matrix metalloproteinase (MMPs) and its inhibitor, tissue inhibitor of metalloproteinase Inhibitors of metalloproteinase (TIMP) degrades a variety of extracellular matrix components and maintains the integrity of the tissue structure and the stability of the internal environment, and maintains a dynamic balance between the two. Once the disturbance is out of balance, it is easy to cause as plaque rupture, and lead to acute coronary syndrome.As plaque around a variety of active cells secreting interferon 纬, interferon 纬 on the process of as has multiple effects, participate in the process mentioned above. Does Lp(a)-IC also cause foam cell formation to participate in the as process? The effect of interferon-纬 on the expression of TIMP in MMPN and the role of interferon-纬 in the expression of TIMP were not reported. Purpose 1. To investigate the effect of Lp(a)-IC on macrophage transformation into foam cells and its involvement in as formation. 2. The effect of LDL-ICL LpAM-IC on the expression of MMP-1 and its inhibitor TIMP-1 mRNA in U937 cells. The effect of interferon 纬 on the MMP-1 expression of U937 cells induced by IC-IFN- 纬 was investigated. Method 1: 1. ICs were prepared by human oxidation, natural LPA) and LDL combined with heterologous anti apoB. The effects of different concentrations of Lp(a)-IC on cholesterol ester accumulation and foam cell formation in mouse peritoneal macrophages were observed. The expression of MMP-1 and TIMP-1mRNA in U937 cells was detected by RT-PCR. U937 cells were treated with different concentrations of interferon 纬 and LDL-IC, and the expression of MMP-1 mRNA in U937 cells was analyzed by RT-PCR.
【学位授予单位】：南京师范大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392;R543

【相似文献】