绞股蓝总皂苷调节THP-1巨噬细胞源性泡沫细胞胆固醇平衡的作用机制

The Mechanism of Gypenosides Regulate Cholesterol Homeostasis in Foam Cells

[目的]通过体外实验研究绞股蓝总皂苷调节THP-1巨噬细胞源性泡沫细胞胆固醇平衡的作用机制。[方法]采用体外培养人THP-1巨噬细胞,以氧化低密度脂蛋白(Oxidized low density lipoprotein,ox-LDL)诱导THP-1巨噬细胞泡沫化为模型,用绞股蓝总皂苷进行干预。通过油红O染色观察细胞内脂质堆积情况和酶比色法定量检测细胞内总胆固醇(TC)和胆固醇酯(CE)的变化,并利用RT-PCR方法检测CD36、ABCA1、LXR-α、PPAR-α受体mRNA表达。[结果]与ox-LDL诱导组相比,绞股蓝总皂苷组(GPS组)巨噬细胞的油红O染色阳性细胞数和细胞内脂质含量均显著减少,同时CD36受体mRNA表达明显降低,而ABCA1、LXR-α、PPAR-α受体mRNA表达明显升高。[结论]绞股蓝总皂苷可抑制ox-LDL诱导的THP-1巨噬细胞泡沫化,降低细胞内脂质积累,促进细胞内的脂质向细胞外转运,有利于防止泡沫细胞的形成及动脉粥样硬化的进程。该作用可能与绞股蓝总皂苷下调巨噬细胞CD36受体表达,上调巨噬细胞ABCA1、LXR-α、PPAR-α受体表达从而减弱巨噬细胞对ox-LDL的摄取和促进脂质的外排有关。

[Objective]The mechanism of Gypenosides regulating cholesterol homeostasis in foam cells was studied through extracorporal experiment.[Methods]The foam cell induced from THP-1 macrophage with ox-LDL was treated with gypenosides.The lipid accumulation in cell was observed by oil red O dyeing and the change of total cholesterol and cholesterol ester in the cells were detected with the enzyme colorimetric quantifies.Then,the receptors' mRNA of CD36,ABCA1,LXR-α and PPAR-α were detected using the method of RT-PCR.[Results]To compare with the induction group of ox-LDL,the positive cell count and the intracellular lipid content of the oil red O dyeing of the macrophages in the foam cell treated with gypenosides were significantly reduced,and the expression of the receptor's mRNA of CD36 was also decreased at the same time,while the expression of the receptors' mRNA of ABCA1,LXR-α,PPAR-α was significantly increased.[Conclusion]Gypenosides can inhibit THP-1 macrophage induced by ox-LDL into foam cells,reduce accumulation of intracellular cholesterol,and promote the transportion of intracellular cholesterol to the extracellular,prevent the formation of foam cell and the process of atherosclerosis.The effect may relate to gypenosides,which downs the expression of the receptor of CD36 in macrophages,upwards the expression of the receptor of ABCA1,LXR-α,PPAR-α in macrophages,and then reduces the intake of ox-LDL in macro-phages,and promotes the transportion of intracellular cholesterol to the extracellular.