依泽替米贝通过小凹蛋白1调节大鼠血管平滑肌细胞内脂质蓄积

Ezetimibe inhibiting intracellular lipid accumulation through caveolin-1 in rat vascular smooth muscle cells

目的:观察依泽替米贝(ezeti mibe)对大鼠血管平滑肌细胞内胆固醇蓄积的影响以及相关的作用机制。方法:以原代培养大鼠血管平滑肌细胞(rat VSMCs)为研究对象,以20 mg/L胆固醇:甲基β环糊精复合物(Chol:MβCD)孵育细胞48 h形成荷脂细胞模型。不同浓度的依泽替米贝(3、10、30μmol/L)处理细胞24 h,或以30μmol/L依泽替米贝分别处理细胞不同时间(0、6、12、24、48 h),HPLC检测细胞内TC、游离胆固醇(FC)的含量,Western blotting检测小凹蛋白1(caveolin-1)蛋白的表达。结果:不同浓度依泽替米贝(3、10、30μmol/L)作用于VSMCs源性荷脂细胞不同时间,细胞内TC、FC的含量呈浓度依赖性减少,以30μmol/L浓度孵育24 h作用最强。Chol:MβCD明显减少细胞caveolin-1蛋白表达水平,依泽替米贝能够逆转这种作用。结论:依泽替米贝抑制Chol:MβCD诱导的大鼠平滑肌细胞中胆固醇蓄积作用可能与caveolin-1有关。

AIM： To determine the effects of ezetimibe on intracellular lipid accumulation and related mechanism in rat vascular smooth muscle cells（VSMCs）. METHODS： VSMCs taken from rat aorta were respectively treated with different concentration of ezetimibe（0,3,10,30 μmol/L）for 24 hours or treated with 30 μmol/L of ezetimibe for different time（0,6,12,24,48 hours）.The concentration of total cholesterol and free cholesterol were detected by high performance liquid chromatography.The expression of caveolin-1 were detected by western blotting.RESULTS：The contents of intracellular total cholesterol（TC） and free cholesterol（FC） were significantly decreased with a peak at 30 μmol/L for 24 h in lipid-loaded cells by ezetimibe in a dose-and time-dependent manner.The level of caveolin-1 protein was elevated 70% by ezetimibe.CONCLUSION： Ezetimibe inhibits cholesterol：methy-β-cyclodextrin（Chol：MβCD）-induced cholesterol accumulation in cultured VSMC through modulating caveolin-1.