氟伐他汀对高糖诱导人足细胞血管内皮生长因子表达的影响及机制

The effect and mechanism of fluvastatin on the expression of vascular endothelial growth factor in human podocytes induced by high glucose

目的探讨氟伐他汀对高糖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,随机分为A组(正常糖组)、B组(高糖组)、C组(高糖+氟伐他汀10-7mol/L组)、D组(高糖+氟伐他汀10-6mol/L组)、E组(高糖+氟伐他汀10-5mol/L组)和F组[高糖+胞外信号调节激酶(ERK)抑制剂PD98059组]。用Western blot检测VEGF和磷酸化ERK1/2(pERK1/2)蛋白表达。结果 B组VEGF、pERK1/2表达较A组明显升高,并呈时间依赖性(P<0.05)。F组VEGF、pERK1/2表达较B组显著降低(P<0.01)。与B组比较,C、D、E组VEGF及pERK1/2表达亦明显减少,并呈浓度依赖性(P<0.05)。结论高糖刺激体外培养人足细胞VEGF表达增加,氟伐他汀可减少高糖诱导的VEGF表达,其机制可能与氟伐他汀抑制ERK信号通路有关。

Objective To investigate the effect and mechanism of fluvastatin on the expression of vascular endothelial growth factor（VEGF） in human podocytes induced by high glucose.MethodsHuman podocytes were randomly divided into six groups of A （normal glucose）,B（high glucose）,C（high glucose plus fluvastatin 10^-7mol/L）,D（high glucose plus fluvastatin 10^-6mol/L）,E（high glucose plus fluvastatin 10^-5mol/L） and F[high glucose plus extracellular signal-regulated kinase（ERK） inhibitor PD98059].The expressions of VEGF and phospho-ERK1/2（pERK1/2） were detected by Western blot.Results The expressions of VEGF and pERK1/2 in group B were increased time-dependently and higher than those in groups of A,C,D,E and F（P〈0.05 or P〈0.01）.Conclusion High glucose increases VEGF expression in human podocytes,which can be decreased by fluvastatin treatment through inhibiting the signaling pathway of ERK.