摘要
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对低氧培养的内皮细胞合成和分泌内皮素-1(ET-1)的影响。方法低氧培养人脐静脉内皮细胞,采用辛伐他汀以不同浓度(0、1、2.5、5.0、10.0μmol/L)和不同作用时间(12、24、48h)进行干预,并用甲羟戊酸(100μmol/L)调节辛伐他汀的作用。采用半定量逆转录聚合酶链反应(RT-PCR)检测内皮细胞ET-1mRNA的表达;采用酶联免疫吸附试验(ELISA)检测内皮细胞上清液中ET-1蛋白的浓度。结果11μmol/L浓度的辛伐他汀对内皮细胞ET-1mRNA和ET-1蛋白表达没有影响,2.5μmol/L辛伐他汀即可抑制ET-1的表达,但与0μmol/L浓度组相比差异无统计学意义;5μmol/L及10μmol/L辛伐他汀则表现出明显的抑制作用(P<0.01),尤以10μmol/L浓度组明显;2以10μmol/L辛伐他汀干预低氧培养的内皮细胞,低氧12h后,内皮细胞ET-1mRNA和ET-1蛋白表达明显减少,24h后继续降低,48h达到最低;3100μmol/L甲羟戊酸可以阻止辛伐他汀对低氧培养的内皮细胞合成和分泌ET-1的抑制作用。结论辛伐他汀对低氧培养的内皮细胞合成和分泌ET-1具有抑制作用。
Objective To observe the role of simvasatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in synthesis and excretion of endothelin-1 （ET-1） in endothelial cell cultured hypoxically. Methods Human umbilical vein endothelial cells were hypoxically cultured and treated with simvastatin by different concentrations （0,1.0,2.5,5.0,10. 0μmol/L） and different times （12,24,48 h）. Mevalonate was used to intervent the effect of simvastatin. Reverse transcription-polymerase chain reaction （RT-PCR）and enzyme-linked immunoadsorbent assay （ELISA） were adopted to measure ET-1 mRNA and ET-1 in supernatant fluid of endothelial cell culture. Results （1）There were no changes of ET-1 mRNA and ET-1 expression after the hypoxically cultured endothelial cell were incubated with 1 μmol/L simvastatin, but ET-1 expression decreased without significant difference compared to control （0 μmol/L simvastatin） when interfered with 2. 5 μmol/Lsimvastatin. The decreases of ET-1 mRNA and ET-1 expression became more obvious when expression were interfered by 5 μmol/Land 10 μmol/L simvastatin（P〈0. 01）. （2） ET-1 mRNA and ET-1 expression decreased at 12 h after the endothelial cells were incubated with 10 μmol/L simvastatin, which became more fewer at 24 h and reached the minimum expression at 48 h （P〈0. 01）. （3） The inhibition effect of simvastatin on ET-1 mRNA and ET-1 expression of endothelial cells could be prevented by mevalonate with concentration of 100 μmol/L. Conclusion Simvastatin can inhibit ET-1 expression in endothelial cell cultured hypoxically.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2008年第1期72-75,共4页
Journal of Sichuan University(Medical Sciences)
