辛伐他汀对血管内皮细胞内皮素-1表达的抑制作用

Supressive effect of simvastatin on endothelin-1 expression in vascular endothelial cell

目的观察羟甲基戊二酰辅酶A(HMG-COA)还原酶抑制剂-辛伐他汀(Simvastatin)对培养的血管内皮细胞表达内皮素-1(ET-1)的影响。方法采用辛伐他汀以不同浓度和不同作用时间对培养的人脐静脉内皮细胞进行干预,并用甲羟戊酸调节辛伐他汀的作用,分别采用半定量逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附试验(ELISA)检测内皮细胞ET-1 mRNA的表达和上清液中ET-1的浓度。结果(1)辛伐他汀以浓度依赖方式抑制内皮细胞ET-1的表达。1μmol/L的辛伐他汀对内皮细胞ET-1 mRNA和ET-1表达没有影响,2.5μmol/L辛伐他汀即表现出抑制作用,5μmol/L及10μmol/L时则更加明显(P<0.01);(2)辛伐他汀以时间依赖方式抑制内皮细胞ET-1的表达。与对照组相比,以10μmol/L辛伐他汀干预内皮细胞12h后,内皮细胞ET-1 mRNA和ET-1表达明显减少,24h后继续减低,36h则更加明显(P<0.01);(3)100μmol/L甲羟戊酸可以阻止辛伐他汀对血管内皮细胞表达ET-1 mRNA和ET-1的抑制作用。结论辛伐他汀可抑制培养的血管内皮细胞合成和分泌ET-1。

Objective To observe the effect of simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on the expression of endothelin-1 （ET-1） in cultured vascular endothelial cell. Methods Cultured human umbilical vein endothelial cells were treated with simvastatin by different concentration and time, and mevalonate was adopted to intervent the effect of simvastatin. Reverse transcription-polymerase chain reaction （ RT-PCR ） and enzyme-linked immunodsordent assay （ELISA） were adopted to measure ET-1mRNA and ET-1 in supernatant fluid of endothelial cell. Results （1） Simvastatin inhibited ET-1 expression of endothelial cell in a concentration-dependent fashion. No change of ET-1mRNA expression and ET-1 level emerged after endothelial cell were incubated with 1 μ mol/L simvastatin, which decreased when intervented by 2.5 μ mol/L simvastatin and became more significant by 5 μ mol/L and 10μ mol/L simvastatin（P〈0.01）. （2） Simvastatin inhibited ET-1 expression of endothelial cell in a time-dependent fashion. ET-1mRNA expression and ET-1 level decreased at 12h after endothelial cells were incubated with 10 μ mol/L simvastatin, which continued to decrease at 24h and became more fewer 36h compared with control group （ P〈0.01 ）. （3） The inhibition effect of simvastatin on ET-1mRNA and ET-1 expression of endothelial cells could be prevented by mevalonate with concentration of 100 μ mol/L. Conclusions Simvastatin can inhibit ET-1 expression of cultured vascular endothelial cell.