丹参酮ⅡA上调ABCA1表达促进泡沫细胞胆固醇流出  

Tanshinone ⅡA up-regulates the expression of ATP-binding cassette transporter A1 and increases cholesterol efflux in RAW 264.7 macrophage-derived foam cells

作　　者：胡海燕[1,2] 李跃艳[2] 李春霞 李兴[4] 陈梦华[4] 周寿红[4] 

机构地区：[1]安化县第二人民医院心内科,湖南安化413522 [2]南华大学附属第一医院心内科,湖南衡阳421001 [3]湖南安化县清塘铺镇计划生育技术服务站,湖南安化413524 [4]南华大学医学院生理学教研室,湖南衡阳421001

出　　处：《国际病理科学与临床杂志》2012年第6期488-495,共8页Journal of International Pathology and Clinical Medicine

摘　　要：目的:探讨丹参酮ⅡA对氧化型低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)诱导的鼠源巨噬细胞性泡沫细胞形成的影响及其机制。方法:体外培养的鼠源性巨噬细胞株,用ox-LDL(50μg/mL)孵育细胞以诱导泡沫细胞,同时用不同质量浓度的丹参酮ⅡA(10-5,10-4和10-3mol/L)处理。用油红O染色观察细胞荷脂情况,高效液相色谱法测定细胞内总胆固醇(total cholesterol,TC)、游离胆固醇(free cholesterol,FC)和胆固醇酯(cholesteryl ester,CE)的水平。采用[3H]标记的胆固醇测定胆固醇流出率。实时定量PCR和Western印迹法分别检测细胞中三磷酸腺苷结合盒转运体A1(ATP-binding cassette transporter A1,ABCA1)的mRNA和蛋白的表达。结果:Ox-LDL处理48 h后,与正常巨噬细胞相比,油红O染色阳性细胞数显著性增加,细胞体积明显增大,细胞内可见大量的脂滴,形态多呈不规则形。与泡沫细胞模型相比,10-4或10-3mol/L丹参酮ⅡA处理组油红O染色阳性细胞数显著减少,细胞内脂滴明显减少,细胞体积明显缩小。与泡沫细胞模型组相比,10-4或10-3mol/L丹参酮ⅡA显著性降低了细胞内TC,FC,CE水平和CE/TC比值,显著性增加了细胞胆固醇流出率和ABCA1mRNA和蛋白的表达。结论:丹参酮ⅡA可抑制ox-LDL诱导的鼠源巨噬细胞性泡沫细胞形成,其机制可能与丹参酮ⅡA增加泡沫细胞中ABCA1的表达,促进胆固醇流出有关。Objective： To investigate the effect oftanshinone low density lipoprotein （ox-LDL） and explore the Ⅱ A on the formation of foam cells induced by the oxidized underlying mechanism. Methods： RAW 264.7 macrophages were incubated with ox-LDL （50 μg/mL） for 48 h to induce foam cells. Cells were treated with tanshinone Ⅱ A （10^-5, 10-4, and 10-3 mol/L） for 48 h at the same time. The cellular lipid accumulation was examined by oilred staining. The level of cellular total cholesterol （TC）, free cholesterol （FC）, and cholesteryl ester （CE） were examined by high performance liquid chromatography assays. Cholesterol efflux from macrophages was tested by cholesterol fabled by [3H]. The mRNA and protein expression of ATP-binding cassette transporter A1 （ABCA1） was detected by Real-time PCR and Western blot, respectively. Results： Oil red O staining positive cells were found and macrophages were filled with lipid droplet in the foam cell model group induced by ox-LDL. Compared withthe foam cells, tanshinoneⅡ A （10^-4 and 10^-3 mol/L） significantly decreased the amount of oil red O staining positive cells and the levels of lipid droplet of foam cells. The levels of TC, FC, CE, and CE/TC ratio in the foam cell model group were significantly increased compared with the control macrophage group. The levels of TC, FC, CE, and CE/TC ratio were significantly decreased. The rate of cholesterol efflux and mRNA and protein expressions of ABCA1 were significantly increased by tanshinone Ⅱ A treatment （10^-4 or 10^-3 mol/L） compared with the foam cell model group. Conclusion： Tanshinone Ⅱ A inhibits the formation of foam cells induced by ox- LDL, which is related to up-regulation of expression ABCA1.

关 键 词：丹参酮ⅡA 泡沫细胞 动脉粥样硬化 胆固醇流出 三磷酸腺苷结合盒转运体A1 

分 类 号：R285[医药卫生—中药学]