PPARγ对THP-1巨噬细胞CD36表达和胆固醇流入的影响

发布时间：2018-07-03 04:25

本文选题：过氧化物酶体增殖物激活型受体Y + CD36　；参考：《南华大学》2005年硕士论文

【摘要】：CD36属于B族清道夫受体,是一种主要的氧化型低密度脂蛋白(oxidized lowdensity lipoprotein,oxLDL)受体。巨噬细胞通过清道夫受体途径吞噬oxLDL,形成富含脂质的泡沫细胞,是动脉粥样硬化(atherosclerosis,As)形成的核心环节。过氧化物酶体增殖物激活型受体γ(peroxisome proliferator-actirated receptorgamma,PPARγ)是核受体超家族成员,作用非常广泛,除参与脂质和脂蛋白代谢、糖代谢平衡外,还涉及脂肪细胞、单核/巨噬细胞等多种细胞的分化,抑制炎症因子生成及炎症过程,与As的发生发展密切相关。在As形成过程中,PPARγ对巨噬细胞内胆固醇和脂质平衡的调控一直是研究的热点。本研究首先在As小型猪动物模型上观察CD36和PPARγ表达的变化;然后在细胞水平上,观察oxLDL对THP-1巨噬细胞CD36表达和胆固醇流入的影响,并采用PPARγ的激动剂ciglitazone和PPARγ反义寡核苷酸处理THP-1巨噬细胞,观察PPARγ对细胞CD36表达及胆固醇流入的影响,初步探讨oxLDL作用的可能机制。第一部分动脉粥样硬化小型猪CD36和PPARγ表达的变化目的在动脉粥样硬化小型猪动物模型上,观察CD36和PPARγ表达的变化。方法采用本研究所建立的As小型猪动物模型,用高脂高胆固醇饲料喂养贵州小香猪12个月,动脉组织切片HE染色观察粥样斑块;采用逆转录-聚合酶链式反应检测CD36及PPARγ mRNA水平;Western印迹检测CD36及PPARγ蛋白质的表达;免疫组织化学法检测CD36蛋白质的表达。结果喂养12个月处死动物,实验组小型猪的主动脉可见As斑块和脂质条纹病变,而在对照组小型猪的主动脉没有发现病变;实验组小型猪的肝组织、肾脏组织和主动脉组织CD36表达上调,同时检测到主动脉组织PPARγ表达上调。
[Abstract]:CD36 belongs to group B scavenger receptor and is a major oxidized low density lipoprotein LDL receptor. Macrophages phagocytosis of oxLDLvia scavenger receptor pathway to form lipide-rich foam cells is the core of atherosclerosis (Atherosclerosis) formation. Peroxisome proliferator activated receptor 纬 (peroxisome proliferator-actirated receptor gamma-PPAR- 纬) is a member of nuclear receptor superfamily. It is involved in lipid and lipoprotein metabolism, glucose metabolism, adipocyte, monocyte / macrophage and other cell differentiation. Inhibition of inflammatory factor production and inflammatory process is closely related to the occurrence and development of as. The regulation of PPAR 纬 on cholesterol and lipid balance in macrophages has been a hot topic in the process of as formation. In this study, the changes of CD36 and PPAR 纬 expression were observed in as miniature pig model, and then the effects of oxLDL on CD36 expression and cholesterol influx in THP-1 macrophages were observed at the cellular level. THP-1 macrophages were treated with ciglitazone and antisense oligodeoxynucleotides. The effects of PPAR- 纬 on CD36 expression and cholesterol influx were observed, and the possible mechanism of oxLDL action was discussed. Part I changes of CD36 and PPAR 纬 expression in Atherosclerotic miniature Pigs objective to observe the expression of CD36 and PPAR 纬 in atherosclerotic miniature pigs. Methods the animal model of as miniature pigs was established in this study. Guizhou Xiao Xiang pigs were fed with high fat and high cholesterol diet for 12 months. The atherosclerotic plaques were observed by HE staining in arterial sections. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of CD36 and PPAR 纬 mRNA. Western blot was used to detect the expression of CD36 and PPAR 纬 protein, and immunohistochemistry was used to detect the expression of CD36 protein. Results the animals were sacrificed for 12 months. The aortic plaques and lipid stripes were found in the aorta of the experimental group, but not in the aorta of the control group, and the liver tissue of the small pig in the experimental group. The expression of CD36 was up-regulated in kidney and aorta, and the expression of PPAR 纬 in aorta was also detected.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R363

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