儿茶酚胺类激素对THP-1细胞泡沫化的影响及其机理的研究

发布时间：2018-07-08 15:33

  本文选题：儿茶酚胺 + 泡沫细胞　； 参考：《四川大学》2005年博士论文

【摘要】：第一部分 心血管系统是心理应激的靶目标,伴有运动诱导的心肌缺血,血压升高,心率增加,心律不齐,动脉粥样硬化的发展,以及死亡。最近的资料指出在下丘脑,垂体腺,肾上腺髓质和交感神经末端之间存在相互作用如同对应激的神经内分泌反应。心理应激导致细胞机能障碍的机制了解甚少,在动脉粥样硬化中表达上调的多种基因,也可被心理应激诱导,精神应激导致细胞功能失调并最终导致心血管疾病的更多的下游信号仍然大部分都未知。 目的:观察儿茶酚胺类激素对THP-1巨噬细胞源性泡沫细胞泡沫化和细胞内胆固醇流出的影响。同时观察儿茶酚胺类激素对THP-1巨噬细胞源性泡沫细胞TGF-β1、CD36、SR-AⅠ、ABCA1、Caveolin-1基因表达的影响。初步了解儿茶酚胺类激素影响THP-1巨噬细胞源性泡沫细胞功能的细胞信号转导途径。 方法:运用高效液相色谱检测细胞内总胆固醇和游离胆固醇的含量,液体闪烁计数器检测细胞内胆固醇流出,逆转录-多聚酶链式反应检测TGF-β1、CD36、SR-AⅠ、ABCA1、Caveolin-1 mRNA的表达,酶联免疫吸附试验检测TGF-β1、Western印迹检测SR-AⅠ和ABCA1蛋白的表达。 结果:不同浓度的去甲肾上腺素(10 nmol/L～10μmol/L)作用THP-1巨噬细胞源性泡沫细胞24小时。结果显示,1μmol/L和10μmol/L去甲肾上腺素处理后,细胞内总胆固醇、游离胆固醇和胆固醇酯明显增加,呈剂量和时间依赖性(p0.05)。而apoA-Ⅰ介导的细胞内胆固醇流出呈时间依赖性减少(p0.05)。100nmol/L及1μmol/L的肾上腺素作用THP-1巨噬细胞源性泡沫细胞后,其TGF-β1、ABCA1 mRNA水平下降(p0.01;p0.05),SR-AⅠmRNA水平升高(p0.05)。100 nmol/L,1μmol/L及10μmol/L的去甲肾上腺素作用THP-1巨噬细胞源性泡沫细胞后,其TGF-β1、ABCA1 mRNA和蛋白水平下降(p0.05);1μmol/L及10μmol/L的去甲肾上腺素则升高SR-AⅠmRNA和蛋白的水平(p0.05)。而肾上腺素和去甲肾上腺素作用细胞后对CD36和Caveolin-1基因表达无影响(p0.05)。为了解去甲肾上腺素影响TGF-β1、SR-AⅠ
[Abstract]:The first part of the cardiovascular system is the target of psychological stress, accompanied by exercise induced myocardial ischemia, elevated blood pressure, increased heart rate, irregular rhythm, The development of atherosclerosis, as well as death. Recent data suggest that there are interactions between hypothalamus, pituitary gland, adrenal medulla and sympathetic nerve terminals as well as neuroendocrine responses to stress. Little is known about the mechanisms of psychological stress leading to cellular dysfunction, and many genes that are up-regulated in atherosclerosis can also be induced by psychological stress. Mental stress causes cell dysfunction and ultimately leads to more downstream signals from cardiovascular disease that remain largely unknown. Aim: to observe the effect of catecholamines on foaming and cholesterol efflux of THP-1 macrophage derived foam cells. Meanwhile, the effects of catecholamines on the expression of Caveolin-1 gene in THP-1 macrophage-derived foam cells were observed. To understand the cellular signal transduction pathway of catecholamines affecting the function of THP-1 macrophage derived foam cells. Methods: the contents of total cholesterol and free cholesterol in cells were detected by high performance liquid chromatography, cholesterol efflux was detected by liquid scintillation counter, and the expression of TGF- 尾 1 CD36A 鈪，

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