丹参酮ⅡA对泡沫细胞胆固醇平衡的影响

Effect of Tanshinone ⅡA on Cholesterol Homeostasis in Foam Cells

目的通过体外细胞实验阐明丹参酮ⅡA对泡沫细胞胆固醇平衡的影响。方法体外培养小鼠RAW264.7细胞,以氧化型低密度脂蛋白诱导为泡沫细胞模型,并用不同浓度的丹参酮ⅡA进行处理,通过油红O染色观察细胞内脂质堆积情况,酶比色法定量检测细胞内总胆固醇和胆固醇酯的变化,荧光定量PCR和WesternBlot检测细胞中CD36、三磷酸腺苷结合盒转运体A1(ABCA1)、肝脏X受体α(LXRα)、过氧化体增殖物激活型受体α(PPARα)及PPARγ的mRNA和蛋白表达。结果 0～20 mg/L的丹参酮ⅡA对泡沫细胞增殖活力无明显影响,20 mg/L丹参酮ⅡA干预后,泡沫细胞内胆固醇酯与总胆固醇的比值显著降低,细胞内脂质累积减少,并上调AB-CA1、LXRα和PPARα的mRNA和蛋白表达,但对CD36表达无明显作用。结论丹参酮ⅡA能抑制泡沫细胞的形成,其机制可能是通过诱导PPARα、LXRα和ABCA1表达,促进胆固醇的外排。

Aim The effect of tanshinone Ⅱ A on cholesterol homeostasis in foam cells was studied in vitro. Methods The foam cell induced from RAW264. 7 macrophage with oxidized low density lipoprotein （ox-LDL） were trea- ted with different concentration of tanshinone Ⅱ A. The relative cell viability were detected by MTr methods, and the change of total cholesterol and cholesterol ester in the cells were detected with the enzyme colorimetric quantifies. The lip- id accumulation in cell was observed by oil red O dyeing, then the expressions of CD36, ATP binding cassette transporter AI （ABCA1）, liver X receptor α （LXRα） and peroxisome proliferator activated receptors γ （PPARγ）, PPARα were de- tected with the methods of fluorescent quantitation PCR and Western Blot. Results The cell viability was not affected when tanshinone Ⅱ A concentrations were in the range of 0 ~ 20 mg/L. The ratio of cholesterol ester and total cholesterol decreased and lipid accumulation decreased when the foam cells were treated with 20 mg/L tanshinone Ⅱ A. Meanwhile, the expression of ABCA1, LXRα, PPARa were increased, but the expression of CD36 had no obvious variance. Con- dusion Tanshinone II A can inhibit the formation of foam cells induced from RAW264. 7 by ox-LDL, the mechanism is possibly related to inducing the expressions of PPARa, LXRa and ABCAI and promoting the excretion of cholesterol.