脂蛋白循環(huán)免疫復(fù)合物致動脈粥樣硬化機(jī)制的研究
本文選題:脂蛋白循環(huán)免疫復(fù)合物 + U937細(xì)胞; 參考:《南京師范大學(xué)》2006年碩士論文
【摘要】:研究背景:氧化修飾脂蛋白在動脈粥樣硬化(Artherosclerosis,As)發(fā)生、發(fā)展中起著重要作用。氧化型低密度脂蛋白(Oxidatized-low density lipoprotein,Ox-LDL)免疫原性發(fā)生改變,在體內(nèi)產(chǎn)生自身抗體并與之結(jié)合,,形成LDL循環(huán)免疫復(fù)合物(immune complex,IC),高LDL-IC水平是As發(fā)生的預(yù)測指標(biāo)。LDL-IC是一種很強(qiáng)的誘導(dǎo)物,經(jīng)FcR γ受體途徑誘導(dǎo)膽固醇酯在人單核巨噬細(xì)胞內(nèi)堆積轉(zhuǎn)化為泡沫細(xì)胞,且效果強(qiáng)于其他途徑;同時(shí)釋放多種細(xì)胞因子、破壞血管內(nèi)皮、誘導(dǎo)平滑肌細(xì)胞增殖,加速As進(jìn)程。高脂蛋白(a)[Lipoprotein(a),Lp(a)]由載脂蛋白(a)[apolipoprotein(a),apo(a)]和apoB通過二硫鍵連接而成,其結(jié)構(gòu)、脂肪酸組成和抗氧化劑含量及體外氧化行為均與LDL相似。As斑塊及人血漿中存在Ox-Lp(a)、自身抗體及其Lp(a)-IC,且冠心病患者Lp(a)-IC水平顯著升高;|(zhì)金屬蛋白酶(matrix metalloproteinase,MMP)及其抑制物組織金屬蛋白酶抑制劑(tissue inhibitors of metalloproteinase,TIMP)降解細(xì)胞外多種基質(zhì)成分,維持組織結(jié)構(gòu)的完整和內(nèi)環(huán)境的穩(wěn)定,兩者之間保持著一種動態(tài)平衡。一旦失衡,易于導(dǎo)致As斑塊破裂,引發(fā)急性冠狀動脈綜合癥(acute coronary syndrome,ACS)。As斑塊周圍多種活性細(xì)胞分泌γ干擾素,γ干擾素對As過程有多重作用,參與上述過程。有關(guān)Lp(a)-IC是否同樣導(dǎo)致泡沫細(xì)胞形成參與As進(jìn)程?對MMP、TIMP表達(dá)的影響,以及γ干擾素在其中的作用等未見報(bào)道。 目的:1.探討Lp(a)-IC對巨噬細(xì)胞轉(zhuǎn)化為泡沫細(xì)胞并參與As形成的影響。2.LDL-IC、Lp(a)-IC對U937細(xì)胞MMP-1及其抑制物TIMP-1 mRNA表達(dá)的影響。3.γ干擾素對IC誘導(dǎo)U937細(xì)胞MMP-1表達(dá)的影響。 方法:1.采用人源的氧化、天然Lp(a)及LDL與異源的抗apoB結(jié)合制備IC,觀察不同濃度的Lp(a)-IC對小鼠腹腔巨噬細(xì)胞膽固醇酯的蓄積和泡沫細(xì)胞形成效果。2.采用不同濃度的LDL、Lp(a)及其IC作用于U937細(xì)胞,RT-PCR分析U937細(xì)胞中MMP-1和TIMP-1mRNA表達(dá)。3.采用不同濃度γ干擾素與LDL-IC共同作用于U937細(xì)胞,通過RT-PCR分析U937細(xì)胞中MMP-1 mRNA表達(dá)。
[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 緯 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 緯, interferon 緯 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-緯 on the expression of TIMP in MMPN and the role of interferon-緯 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 緯 on the MMP-1 expression of U937 cells induced by IC-IFN- 緯 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 緯 and LDL-IC, and the expression of MMP-1 mRNA in U937 cells was analyzed by RT-PCR.
【學(xué)位授予單位】:南京師范大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2006
【分類號】:R392;R543
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