氟伐他汀联合氯沙坦对血管紧张素Ⅱ诱导的人足细胞血管内皮生长因子表达的影响及机制研究  

Effect of combination of fluvastatin and losartan on the expression of vascular endothelial growth factor induced by angiotensin Ⅱ in human podocytes and associated mechanism

作　　者：刘佳[1] 王笑云 徐亚光[1] 刘艳春[1] 卞帅博[1] 赵鲁米[1] 赵秀芬[1] 钱军[1] 邢昌赢[1] 

机构地区：[1]南京医科大学第一附属医院(江苏省人民医院)肾内科,210029 [2]南京明基医院肾内科

出　　处：《中华肾脏病杂志》2012年第9期710-714,共5页Chinese Journal of Nephrology

基　　金：江苏省卫生厅科研基金（H200317）

摘　　要：目的 探讨氟伐他汀联合氯沙坦对血管紧张素Ⅱ（ AngⅡ）诱导的人足细胞血管内皮生长因子（VEGF）表达的影响及机制.方法 体外培养人足细胞株,采用不同浓度的AngⅡ（10-9～10-5mol/L）刺激人足细胞,另予氟伐他汀（10-7、10-6、10-5 mol/L）和（或）氯沙坦（10-7、10-6、10-5 mol/L）、ERK特异性阻断剂PD98059（ 5× 10-5 mol/L）干预.Western印迹法检测VEGF、磷酸化（p）ERK1/2蛋白的表达.RT-PCR法检测VEGF mRNA的表达.结果 AngⅡ刺激后,人足细胞VEGF mRNA和蛋白的表达显著增加（P＜0.05）,p-ERK1/2增加（P＜0.05）.氟伐他汀、氯沙坦及PD98059均可下调AngⅡ诱导的VEGF mRNA和蛋白表达及ERK1/2磷酸化（P＜0.05）,而氟伐他汀和氯沙坦联合干预较单独作用抑制效果更为显著（P＜0.01）.结论 氟伐他汀和氯沙坦均可抑制AngⅡ诱导足细胞VEGF的过表达,且两者联合具有协同作用.抑制ERK信号通路可能是实现其联合作用的机制之一.Objective To explore the effect and associated mechanism of fluvastatin combined with losartan on the expression of vascular endothelial growth factor （VEGF） in human podocytes induced by angiotensin （Ang）Ⅱ.Methods The differentiated human podocytes were cultured with various concentrations of Ang Ⅱ （10-9 to 10-5 mol/L） in vitro,followed by treatment of fluvastatin （10-7,10-6 and 10-5 mol/L）,losartan （10-7,10-6 and 10-5 mol/L）,extracellular signal-regulated kinase （ERK） inhibitor PD98059,and combination of fluvastatin and lolsartan.Expressions of VEGF and phosphorylation （p）ERK1/2 protein in podocytes were detected by Western blotting.RT-PCR was used to examine VEGF mRNA expression （P〈0.01）.Results Ang Ⅱ up-regulated the expressions of VEGF and p-ERK1/2 in time-and dose-dependent manner.Above elevated expressions of VEGF and p-ERK1/2 induced by Ang Ⅱ could be down-regulated by fluvastatin,losartan and PD98059 respectively （P〈0.05）.More obvious reduction of above expressions was found in combination of fluvastatin and losartan as compared to single agent （P 〈0.05）.Conclusions Either fluvastatin or losartan can down-regulate the over-expression of VEGF and p-ERK1/2 induced by Ang Ⅱ in human podocytes,and their combination has a cooperative effect.The ERK signaling pathway may be one of the mechanisms of their renal protective effects.

关 键 词：洛沙坦 氟伐他汀 血管内皮生长因子类 糖尿病肾病 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]