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
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江苏省卫生厅科研基金资助(H200317)


Effects of fluvastatin and losartan on vascular endothelial growth factor biosynthesis in human podocyte treated by angiotensin Ⅱ
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    目的:观察氟伐他汀及氯沙坦对血管紧张素Ⅱ(angiotensin Ⅱ,AngⅡ)刺激人足细胞血管内皮细胞生长因子(vascular 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(10-6~10-4 mol/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-

    Abstract:

    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 AngⅡfor 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 AngⅡ(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:①VEGF synthesis by human podocyte cultured in AngⅡ medium increased obviously at the concentration of 10-7 mol/L after 24 h. ②Fluvastatin or losartan inhibited VEGF expression stimulated by AngⅡ,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 AngⅡ 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.

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卞帅博,刘 佳,孙 彬,赵秀芬,钱 军,邢昌赢,王笑云.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[J].南京医科大学学报(自然科学版),2011,(8):1123-1127

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  • 收稿日期:2011-04-17
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