氟伐他汀及氯沙坦对血管紧张素Ⅱ诱导人足细胞VEGF表达的影响

Effects of fluvastatin and losartan on vascular endothelial growth factor biosynthesis in human podocyte treated by angiotensin Ⅱ

目的:观察氟伐他汀及氯沙坦对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)刺激人足细胞血管内皮细胞生长因子(vascu-lar endothelial growth factor,VEGF)表达的影响。方法:采用不同浓度的(10-9～10-5 mol/L)AngⅡ刺激人足细胞24 h以确定最适干预浓度;选择最适干预浓度(10-7 mol/L)的AngⅡ刺激0、6、12、24 h以确定最适干预时间;AngⅡ(10-7 mol/L)和不同浓度的(10-7～10-5 mol/L)氟伐他汀共同干预足细胞24 h以确定氟伐他汀最适干预浓度;AngⅡ(10-7 mol/L)和不同浓度的(10-6～10-4mol/L)氯沙坦共同干预足细胞24 h以确定氯沙坦最适干预浓度;氟伐他汀和氯沙坦(均为10-6 mol/L)共同干预足细胞24 h。Western blot检测人足细胞VEGF的表达。结果:①10-7 mol/L AngⅡ刺激人足细胞24 h后表达VEGF增加最明显;②氟伐他汀干预组与AngⅡ刺激组比较,VEGF表达明显下降,浓度10-5 mol/L下降最明显。氯沙坦干预组与AngⅡ刺激组比较,VEGF表达明显下降,浓度10-4 mol/L下降最明显;③10-6 mol/L氟伐他汀和10-6 mol/L氯沙坦共同干预人足细胞后,VEGF表达下降比氟伐他汀、氯沙坦单药干预组更明显(P<0.01)。结论:AngⅡ促进人足细胞表达VEGF,具有一定的时间和浓度依赖性,氟伐他汀和氯沙坦均可抑制此作用,且二者具有协同抑制效应。

Objective：To investigate the effects of fluvastatin and losartan on vascular endothelial growth factor（VEGF） biosynthesis by human podocyte treated with angiotensin Ⅱ（AngⅡ）.Methods：Cultured human podocytes were incubated with AngⅡ for 24 h at the concentration from 10-9 to 10-5 mol / L to choose the suitable concentration,and the optimal treatment time were chosed at the AngⅡ concentration of 10-7 mol / L after treated different times（0,6,12 and 24 hours）.The podocytes were incubated with Ang Ⅱ（10-7 mol / L） and different concentrations of fluvastatin（10-7 ～10-5 mol / L） for 24 h to choose the suitable concentration of fluvastatin.Then the podocytes were incubated with AngⅡ（10-7 mol / L） and different concentrations of losartan（10-6 ～10-4 mol / L） for 24 h to choose the suitable concentration of losartan.Finally,the podocytes were incubated by AngⅡ（10-7 mol / L） with fluvastatin and losartan（both 10-6 mol / L）,and VEGF expression was detected using Western bolt.Results： ① VEGF synthesis by human podocyte cultured in Ang Ⅱ medium increased obviously at the concentration of 10-7 mol / L after 24 h.② Fluvastatin or losartan inhibited VEGF expression stimulated by Ang Ⅱ,and the 10-5 mol / L of fluvastatin and the 10-4 mol / L of losartan had the most siginificant effect.③Fluvastatin（10-6 mol / L） combined with losartan（10-6 mol / L） inhibited VEGF expression more siginificantly than the effect of each alone.Conclusion：It is suggested that Ang Ⅱ stimulates VEGF biosynthesis by human podocyte in a time and concentration pattern.Both fluvastatin and losartan can inhibit this effect,and they have synergistic inhibitory effects.