GDF15对氧化应激诱导血管内皮损伤和血管生成的调节作用

Regulatory effects of GDF15 on oxidative stress-induced vascular endothelial injury and an⁃giogenesis

目的:探讨生长转化因子15(GDF15)对过氧化氢(H_(2)O_(2))诱导的内皮细胞损伤和血管生成的影响。方法:用H_(2)O_(2)诱导人脐静脉内皮细胞(HUVECs)氧化损伤模型,分为对照组、H_(2)O_(2)组、小分子干扰RNA(siRNA)靶向沉默GDF15(si-GDF15)组和si-GDF15+H_(2)O_(2)组。采用CCK-8检测细胞存活率,流式细胞术检测细胞活性氧(ROS)的浓度和凋亡率,划痕实验检测细胞迁移能力,小管形成实验检测内皮细胞成管能力。结果:与对照组比较,H_(2)O_(2)组细胞ROS浓度和凋亡率显著增高,细胞增殖、迁移和小管生成能力显著降低(均P<0.05);与H_(2)O_(2)组比较,si-GDF15+H_(2)O_(2)组细胞ROS和凋亡率显著增高,细胞增殖、迁移和小管生成能力显著降低(均P<0.05)。结论:沉默GDF15能增强H_(2)O_(2)诱导的内皮损伤,并抑制HUVECs的血管形成能力。

Objective:To investigate the effects of growth differentiation factor 15(GDF15)on hydrogen peroxide(H_(2)O_(2))-induced endothelial cell injury and angiogenesis.Methods:Human umbilical vein endothelial cells(HUVECs)models of H_(2)O_(2)-induced oxidative injury were established,and the cells were divided into control group,H_(2)O_(2) group,small interfering RNA(siRNA)-targeted silencing of GDF15(si-GDF15)group and si-GDF15+H_(2)O_(2) group.CCK8 was used to detect cell survival,flow cytometry was used to detect the concentration of reactive oxygen species(ROS)and apoptosis rate,scratch assay was used to detect cell migration ability,and tubule formation assay to detect the tube-forming ability of endothelial cells.Results:Compared with the control group,the ROS concentration and apoptosis rate of cells were significantly increased in the H_(2)O_(2) group,whereas the proliferation,migration and tube-forming ability of cells were significantly decreased(P<0.05).Compared with the H_(2)O_(2) group,the ROS level and apoptosis rate of cells were significantly increased in the si-GDF15+H_(2)O_(2) group,while the proliferation,migration and tube-forming ability of cells were significantly decreased(P<0.05).Conclusion:Silencing GDF15 aggravates H_(2)O_(2)-induced endothelial injury and inhibits the angiogenic ability of HUVECs.