培哚普利对U937泡沫细胞血管内皮生长因子表达与分泌的影响

Effect of perindopril on the expression and protein excretion of vascular endothelial growth factor in U937 foam cells

目的观察培哚普利对泡沫细胞血管内皮生长因子(VEGF)mR-NA表达与蛋白分泌的影响。方法以氧化型低密度脂蛋白刺激体外培养的人单核细胞株U937细胞,建立U937泡沫细胞模型。再用不同浓度的培哚普利(0.01μM、0.1μM、1μM)进行干预。RT-PCR检测泡沫细胞VEGF mRNA表达,ELISA检测泡沫细胞VEGF蛋白的分泌。结果U937泡沫细胞VEGF mRNA表达和VEGF蛋白分泌[2.371±0.253,(1 804.18±177.59)pg/ml]增加,与U937细胞组[0.954±0.245,(716.19±60.82)pg/ml]相比,差异有显著统计学意义(均P<0.01)。培哚普利干预后,U937泡沫细胞VEGF mRNA表达水平呈浓度依赖性降低(2.068±0.270、1.533±0.248、1.022±0.189);VEGF蛋白分泌[(1601.46±154.68)pg/ml、(1 377.09±110.36)pg/ml、(1 017.89±147.18)pg/ml]也呈浓度依赖性降低,差异有显著统计学意义(均P<0.01)。结论氧化型低密度脂蛋白可刺激U937细胞成为泡沫细胞;其VEGFmRNA表达、蛋白分泌水平较U937细胞显著性增加;培哚普利干预U937泡沫细胞,可使其VEGF mRNA表达与蛋白分泌呈浓度依赖性降低。

Objective To study the effects of pefindopril on the levels of vascular endothelial growth factor（VEGF） mRNA expression and protein excretion in the U937 foam cells. Methods Human monocyte line cells U937 were incubated with ox-LDL and a macrophage-derived foam cell model was established. Then ,they were treated with perindopril（0. 01 μM ,0. 1 μM, 1μM）. The levels of VEGF mRNA and protein in the U937 cells and the U937 foam cells were measured by RT-PCR and ELISA. Results VEGF mRNA levels（2. 371 ± 0. 253 vs. 0. 954 ± O. 245 ,P 〈 0. O1 ） and VEGF protein levels（ 1804. 18 ± 177. 59 vs. 716. 19 ± 60. 82 pg/ml, P 〈 0. 01 ） in the U937 foam cells increased significantly, compared with control cells. Treated with perindopril（0. 01 μM,0. 1 p,M, 1 p,M）,VEGF mRNA levels and VEGF protein levels were concentration-depently attenuated, VEGF mRNA levels foam cells vs perindopril treated cells （2. 371 ± 0. 253 vs. 2. 068 ± 0. 270,1. 533 ± 0. 248,1. 022 ± 0. 189, P 〈 0. 01, respectively）, VEGF protein levels foam cells vs perindopril treated cells （ 1804. 18 ± 177.59 vs. 1 601.46 ± 154. 68,1 377.09 ± 110. 36,1 017.89 ± 147. 18 pg/ml,P 〈0. 01 ,respectively）. Conclusions Ox-LDL can induce human monoeyte line U937 cells into foam cells. VEGF mRNA expression and protein excretion levels in foam cells increased significantly. Perindopril can attenuated VEGF mRNA expression and protein secretion in foam cells.