辛伐他汀对THP-1巨噬细胞胆固醇外流及ABCA1、CD36表达影响
Effect of simvastatin on cholesterol efflux and expression of ABCA1 and CD36 in THP-1 macrophages
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摘要: 目的 研究不同剂量辛伐他汀对氧化型低密度脂蛋白(ox-LDL)诱导的THP-1巨噬细胞胆固醇外流及ATP结合盒受体A1(ABCA1)、CD36表达的影响。 方法 建立ox-LDL诱导泡沫细胞模型,THP-1巨噬细胞体外培养,用辛伐他汀进行干预,用3H标记胆固醇,液体闪烁计数法检测胆固醇外流量,油红O染色观察细胞泡沫化程度,Western Blot、RT-PCR检测细胞内ABCA1及CD36蛋白和mRNA表达。 结果 辛伐他汀组较ox-LDL诱导组胆固醇外流明显增加,ABCA1受体蛋白及mRNA表达明显增加(P<0.05),同时CD36受体蛋白及mRNA表达明显下调(P<0.05)呈剂量依赖性。 结论 辛伐他汀可促进ox-LDL诱导的泡沫细胞胆固醇外流,抑制巨噬细胞泡沫化,该作用可能与辛伐他汀上调ABCA1及抑制CD36表达有关。Abstract: Objective To study the effect of different simvastatin doses on cholesterol efflux induced by oxidized low density lipoprotein(ox-LDL) and expression of ABCA1 and CD36 in THP-1 macrophages. Methods A model of ox-LDL-induced foam cells was established.THP-1 macrophages were cultured in vitro,treated with simavastatin,and labeled with 3H.Cholesterol efflux was measured by liquid scintillation.Formation of foam cells was observed with oil red O staining.Expressions of ABCA1 and CD36 protein and mRNA were detected by Western blot and RT-PCR,respectively. Results The cholesterol efflux volume and the expression level of ABCA1 protein and mRNA were significantly higher while the expression level of CD36 protein and mRNA was significantly lower in simvastatin treatment group than in ox-LDL induction group(P<0.05). Conclusion Simvastatin can promote ox-LDL-induced cholesterol efflux from foam cells and inhibit formation of foam macrophages by up-regulating ABCA1 expression and down-regulating CD36 expression.