依折麦布与瑞舒伐他汀对平滑肌源性泡沫细胞小凹蛋白-1 mRNA表达的影响

Effects of ezetimibe and rosuvastatin on the expression of Caveolin-1 mRNA in smooth muscle derived foam cells

目的研究依折麦布联合瑞舒伐他汀对氧化低密度脂蛋白(ox-LDL)诱导的平滑肌源性泡沫细胞小凹蛋白-1(Caveolin-1) mRNA表达的影响。方法将大鼠胸主动脉VSMCs分为9个组,分别为空白对照组、泡沫细胞组、不同浓度的依折麦布组(3、10、30μmol/L)、不同浓度的瑞舒伐他汀组(0. 1、1. 0、5. 0μmol/L)、联合组(依折麦布30μmol/L+瑞舒伐他汀5. 0μmol/L),油红O染色鉴定泡沫细胞模型,real-time PCR检测各组细胞Caveolin-1 mRNA表达。结果与空白对照组相比,泡沫细胞组Caveolin-1 mRNA表达降低[(0. 248 7±0. 042 0) vs (1. 004 1±0. 017 1)],差异有统计学意义(P <0. 05);与泡沫细胞组相比,不同浓度的依折麦布组[(0. 371 3±0. 025 2)、(0. 489 8±0. 027 9)、(0. 726 1±0. 029 1)]及瑞舒伐他汀组[(0. 460 2±0. 022 8)、(0. 623 7±0. 028 8)、(0. 751 8±0. 043 1)]Caveolin-1 mRNA表达增加,各组间差异有统计学意义(P <0. 05),且呈一定浓度依赖性(P <0. 05);且联合组(0. 937 6±0. 029 7)与单药组比较,Caveolin-1 mRNA表达增加,差异有统计学意义(P <0. 05)。结论依折麦布及瑞舒伐他汀均促进平滑肌源性泡沫细胞中胆固醇的逆向转运(RCT),此过程可能通过上调Caveolin-1 mRNA的表达实现;且两者联合此作用更显著。

Objective To investigate the influence of ezetimibe combined with rosuvastatin on expression of Caveolin-1 in smooth muscle derived foam cells induced by oxidized low density lipoprotein(oxLDL).Methods The rat thoracic aortic smooth muscle cells(VSMCs)were selected from generations 3-5 in logarithmic growth cycle.The rat vascular smooth cells were induced using oxidized low density lipoprotein(ox-LDL 50μg/ml for 48 h)to establish foam cell model.The normal cultured rat thoracic aortic smooth muscle cells were used as blank control group.Foam cells were divided into foam cell group,different concentrations of ezetimibe group,different concentrations of rosuvastatin group,combination group.The foam cells were incubated with different doses of ezetimibe(3.0,10.0,30.0μmol/L)or rosuvastatin(0.1,1.0,5.0μmol/L)for 24 h,or cultured with rosuvastatin 5.0μmol/L+ezetimibe 30.0μmol/L in combination groups.Oil red 0 staining was used to identify foam cell models.The expression of Caveolin-1 mRNA was detected by real-time fluorescent quantitative polymerase chain reaction(qRT-PCR).Results Compared with blank control group,the mRNA expression of Caveolin-1 in foam cell group were decreased significantly((0.248 7±0.042 0)vs(1.004 1±0.017 1),P<0.05)Compared with foam cell group,the mRNA expression of Caveolin-1 was increased in a dose-dependent manner in ezetimibe group and rosuvastatin group[(0.371 3±0.025 2),(0.489 8±0.027 9),(0.726 1±0.029 1)vs(0.248 7±0.042 0);(0.460 2±0.022 8),(0.623 7±0.028 8),(0.751 8±0.043 1)vs(0.248 7±0.042 0),P<0.05].Compared with the ezetimibe(30.0μmol/L)and the rosuvastatin(5.0μmol/L),the mRNA expression of Caveolin-1 in combined group were increased,the difference was statistically significant((0.726 1±0.029 1),(0.751 8±0.043 1)vs(0.937 6±0.029 7),P<0.05)Conclusions Ezetimibe and rosuvastatin can promote the reverse transport of cholesterol(RCT)in smooth muscle derived foam cells by upregulating expression of Caveolin-1 mRNA.And the combination of ezetimibe(30.0μmol/L)and rosuvastatin(5.0μmol/L)has more significant effect.