氟伐他汀对人脐静脉内皮细胞游离钙离子水平及内皮型一氧化氮合酶活性的影响

目的:观察氟伐他汀对人脐静脉内皮细胞(HUVECs)游离钙离子水平及内皮型一氧化氮合酶(eNOS)活性的影响及可能机制。方法:体外培养HUVECs,随机分为5组:空白对照组,氟伐他汀(10-8,10-7,10-6,10-5mol/L)组。采用硝酸还原酶法测定细胞上清液中NO含量,液体闪烁计数仪测定L-3H]-精氨酸和L-3H]-瓜氨酸的含量,用激光共聚焦扫描显像系统检测内皮细胞内游离钙离子浓度(Ca2 ]i)水平的变化。结果:与空白对照组比较,10-8,10-7,10-6,10-5mol/L氟伐他汀孵育细胞12h后可显著升高HUVECs细胞内eNOS活性,促进NO释放,同时伴有Ca2 ]i升高,且呈浓度依赖性。另外,10-5mol/L氟伐他汀在0～12h时间段呈时间依赖性增高eNOS活性,作用12h使eNOS活性达到最高(P<0.01)。结论:氟伐他汀呈浓度依赖性升高HUVECseNOS活性和促进NO释放,该作用与其增加内皮细胞内Ca2 ]i有关。

Effects of Fluvastatin on the intracellular Ca2+ level and endothelial nitric oxide synthase activity in cultured human umbilical vein endothelial cells

Objective:To investigate the effect of fluvastatin on the intracellular Ca2 level and endothelial nitric oxide synthase(eNOS)activity in cultured human umbilical vein endothelial cells(HUVECs).Method:Cultured HUVECs were randomly divided into 5 groups:control,fluvastatin(10-8-10-5 mol/L).Nitric oxide(NO)was measured by colorimetry.L-3H]-arginine and L-3H]-citrulline were measured by scinillation counting.Ca2 ]i was observed by laser-scanning confocal microscope.Result:Incubation HUVECs with 10-8-10-5 mol/L fluvastatin for 12 h increased intracellular Ca2 level,eNOS activity and NO release in a concentration-dependent manner.In addition,10-5 mol/L fluvastatin improved eNOS activity in a time-dependent way at different time(0,6,12 h),and eNOS activity was most promoted by fluvastatin after 12 h incubation.Conclusion:Fluvastatin dose-dependently increases HUVECs eNOS activity and NO release,which is related to increased intracellular Ca2 level.