高糖腹透液对腹膜间皮细胞分泌VEGF的影响及氟伐他汀的干预作用

The effect of high-glucose peritoneal dialysate and fluvastatin on the expression of vascular endothelial growth factor in human peritoneal mesothelial cells

目的:观察氟伐他汀(fluvastatin,Flu)对高糖腹透液(high-glucose peritoneal dialysate,HGPDS)诱导的人腹膜间皮细胞(human peritoneal mesothelial cells,HPMCs)分泌血管内皮生长因子(vascular endothelial growth factor,VEGF)的影响。方法:体外培养HPMCs,同步化48 h后,分组如下:正常对照组、HGPDS组、HGPDS+Flu组、单纯Flu组。倒置显微镜观察各组细胞形态,RT-PCR法检测各组VEGF的mRNA表达,Western blot检测各组VEGF蛋白的表达。结果:与正常对照组相比,在HGPDS作用下,48 h后细胞由铺路石样转变为长梭形,1×10-6mol/L Flu可部分逆转HPMCs的形态改变。与正常对照组相比,在HGPDS作用下,人腹膜间皮细胞VEGF mRNA及蛋白表达明显增多(P<0.05),并呈时间依赖性,VEGF mRNA和蛋白分别在HGPDS干预后12 h和48 h达高峰(P<0.05)。Flu可明显抑制HGPDS诱导的VEGF的表达(P<0.05),并呈浓度依赖性。结论:适当浓度的Flu可以抑制HGPDS刺激体外培养人腹膜间皮细胞VEGF表达增加。

Objective：To explore the effect of high-glucose peritoneal dialysate（HGPDS） and fluvastatin（Flu） on the expression of vascular endothelial growth factor（VEGF） in human peritoneal mesothelial cells（HPMCs）.Methods：After incubated in DMEM with 0.01% FBS for 48 h,HPMCs were randomly divided as follows：control group,HGPDS group,HGPDS＋Flu group,Flu alone group.The phenotype changes of HPMCs were observed by light microscopy.The mRNA expression of VEGF was observed by RT-PCR.HPMCs were treated for 48 h and the levels of VEGF protein were measured by Western blot.Results：Compared with the normal control group,after incubation with HGPDS for 48 h,the cell morphology was changed from a typical cobblestone-like appearance to fibroblast-like appearance.Flu（1 × 10-6） mol/L could partially improved the cell morphology changed by HGPDS.The mRNA and protein expressions of VEGF increased time dependently in HPMCs treated with HGPDS（P〈0.05）,which peaked at 12 h and 48 h,respectively.Flu significantly inhibited the effects of HGPDS on the expression of VEGF in a dose-dependent manner（P〈0.05）.Conclusion： Flu could decrease VEGF expression in HPMCs which was induced by HGPDS.