【作者】 曾颖；

【导师】 易光辉；

【作者基本信息】 南华大学 ， 病理学与病理生理学， 2006， 硕士

【摘要】 研究背景：清道夫受体介导的氧化低密度脂蛋白的蓄积是动脉粥样硬化发生发展中泡沫细胞形成的关键。CD36属于B类清道夫受体，丰富表达于单核巨噬细胞膜表面，它是一种主要的oxLDL受体。过氧化物酶体增殖物激活型受体)γ(peroxisomeproliferators-activated receptor-γ，PPARγ)是核受体超家族成员之一，作用范围非常广，其主要功能是调节基因转录。PPARγ是一种核转录因子，具有多种上游调控作用，既可控制炎症反应，亦可诱导CD36基因的表达。研究提示，oxLD啦过激活PPARγ上调巨噬细胞CD36的基因表达。研究显示，PPARγ-CD36信号通路在单核巨噬细胞对氧化低密度脂蛋白(ox-LDL)的摄取、泡沫细胞形成过程中起到重要作用。PPARγ的转录活性受翻译后机制磷酸化的调节，研究表明，PPARγ-Pi是其靶基因的负向调节因子。阿托伐他汀(atorvastatin)除具有显著的降脂作用外，还具有独特的心血管疾病预防作用，如抑制炎症、稳定粥样斑块、改善内皮功能、抗血小板聚集、抑制血管平滑肌细胞增殖、抑制LDL的氧化修饰、抑制清道夫受体表达等作用。本研究意在探讨阿托伐他汀对THP-1巨噬细胞脂质蓄积的影响及其影响机制。 目的：观察阿托伐他汀对THP-1巨噬细胞胆固醇流入及CD36表达的影响，阿托伐他汀对ox-LDL诱导的THP-1巨噬细胞脂质蓄积及CD36、PPARγ表达的影响，阿托伐他汀、PPARγ激动剂与拮抗剂对THP-1巨噬细胞胆固醇蓄积及CD36、PPARγ,表达及对PPARγ磷酸化水平的影响。更多还原

【Abstract】 BACGROUND Scavenger receptor-mediated accumulation of oxLDL-C is considered to be a critical step in the development of atherosclerotic foam cell formation. The class B scavenger receptor, CD36, is identified as the major receptor for oxidized low density lipoprotein(oxLDL). Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of nuclear hormone receptor superfamily. PPARγ has been implicated in such diverse pathways as lipid metabolism and glucose homeostasis, promoting adipocyte, monocyte/macrophage differentiation, inhibiting inflammation. PPARy heterodimerizes with the retinoid X receptor (RXR) and functions as a transcriptional regulator of genes that modulate lipid metabolism and adipocyte gene expression. OxLDL could upregulate CD36 expression by activating PPARγ in THP-1 macrophage. PPARγ -CD36 pathway plays an important effect in oxLDL-uptake of THP-1 macrophage and atherosclerotic foam cell formation. Atorvastatin has various effects in preventing and treating cardiovascular diseases, such as endothelial normalization, anti-inflammatory effects, inhibition of LDL oxidation, stabilization of atherosclerotic plaque, inhibition of platelet thrombus formation and the scavenger receptor expression. The study is aimed to investigate the effect of atorvastatin on THP-1 macrophage lipid accumulation and the possible mechanism.OBJECTIVE To investigate the effects of atorvastatin on cholesterol influx and CD36 expression in THP-1 macrophages, the effects of atorvastatin on oxLDL-induced lipid accumulation and CD36, PPARγ expression in THP-1 macrophages, the effects atorvastatin , PPARγ agonist and antagonist on cholesterol accumulation and the expression of CD36, PPAR γ and PPARγ -Pi in THP-1 macrophages.METHODS THP-1 macrophages were induced to differentiation into macrophages by更多还原