他汀基团修饰的新型自组装短肽对ox-LDL诱导血管内皮细胞损伤的保护效应及分子机制

The protective effect of self-assembling peptide modified by statins on ox-LDL induced vascular endothelial cells injury and the molecular mechanism

目的探讨他汀基团修饰的新型自组装短肽(statins-SAP)对氧化低密度脂蛋白(ox-LDL)诱导血管内皮细胞损伤的保护效应及分子机制。方法将人脐静脉内皮细胞分为5组并给予含不同试剂的DMEM完全培养基培养:对照组(磷酸盐缓冲液)、ox-LDL组(200 mg/L ox-LDL)、洛伐他汀组(200 mg/L ox-LDL+10 mg/L洛伐他汀原料药)、statins-SAP组(200 mg/L ox-LDL+150 mg/L statins-SAP)、信号通路组(200 mg/L ox-LDL+150 mg/L statins-SAP+25μmol/L信号通路抑制剂LY450139)。检测并比较各实验组细胞活力、细胞迁移能力、细胞凋亡率、血管内皮生长因子(VEGF)/Notch通路基因表达、凋亡基因蛋白表达等。结果与洛伐他汀组比较,statins-SAP组能明显改善ox-LDL对细胞造成的损伤,细胞活力及细胞迁移能力均明显增强(均P<0.05)。各实验组细胞中B淋巴细胞瘤-2(Bcl-2)、VEGF、血管内皮生长因子受体2(VEGFR-2)基因相对表达量和Bcl-2、VEGFR-2的蛋白相对表达量比较,ox-LDL组低于对照组(均P<0.05),statins-SAP组高于ox-LDL组和信号通路组(均P<0.05)。各实验组细胞中Bax、Notch1、DLL4基因相对表达量和Bax、Notch1的蛋白相对表达量比较,ox-LDL组高于对照组(均P<0.05),statins-SAP组低于ox-LDL组和信号通路组(均P<0.05)。结论statins-SAP通过激活VEGF/Notch信号通路减轻ox-LDL诱导的血管内皮细胞损伤。

Objective To investigate the protective effect of self-assembling peptide modified by statins(statins-SAP)on oxidized low density lipoprotein(ox-LDL)induced vascular endothelial cells injury and the molecular mechanism.Methods Human umbilical vein endothelial cells were divided into five groups and cultured in DMEM medium containing different reagents:control group(phosphate buffer solution),ox-LDL group(200 mg/L ox-LDL),lovastatin group(200 mg/L ox-LDL and 10 mg/L lovastatin),statins-SAP group(200 mg/L ox-LDL and 150 mg/L statins-SAP)and signaling pathway group(200 mg/L ox-LDL,150 mg/L statins-SAP and 25μmol/L VEGF/Notch signaling pathway inhibitor LY450139).The cell viability,mobility and apoptosis rate,the expression of VEGF and Notch pathway gene and the expression of apoptosis protein were detected and compared.Results Compared with lovastatin group,ox-LDL-induced cell injury was significantly decreased and cell viability and cell migration capacity were significantly enhanced in statins-SAP group(P<0.05).The relative expression of B lymphoma-2(Bcl-2),VEGF,vascular endothelial growth factor receptor 2(VEGFR-2)gene and protein expression of Bcl-2 and VEGFR-2 were significantly lower in ox-LDL group than in the control group(P<0.05),and significantly higher in statins-SAP group than in ox-LDL group and signal pathway group(all P<0.05).The relative expression of Bax,Notch1,DLL4 gene and protein expression of Bax,Notch1 were significantly higher in ox-LDL group than in the control group(P<0.05),and significantly lower in statins-SAP group than in ox-LDL group and signal pathway group(all P<0.05).Conclusion Statins-SAP alleviates ox-LDL-induced vascular endothelial cell injury by activating VEGF/Notch pathway.