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目的 研究血管紧张素II(AngII)和AngIII型受体 (AT1)拮抗剂缬沙坦对人脐静脉内皮细胞 (HUVECs)血凝素样氧化低密度脂蛋白受体 (LOX 1)基因转录和蛋白表达的影响 ,以进一步探讨AngII和LOX 1在动脉粥样硬化 (AS)中的地位和相互关系 ,以及缬沙坦可能的抗AS作用。方法 将不同浓度AngII(1× 10 -5～ 1× 10 -10 mol/L)与HUVECs共孵育 2 4h ,以及将 1× 10 -6mol/L浓度的AngII与HUVECs作用不同时间 (0、3、6、12、2 4、36、4 8h)后 ,用细胞酶联免疫法和半定量RT PCR分别检测LOX 1蛋白和mRNA表达的情况 ,并观察缬沙坦对此的影响。结果 AngII呈浓度依赖方式诱导HUVECsLOX 1蛋白和mRNA表达增加 ;10 -6mol/L的AngII作用 3h ,内皮细胞LOX 1蛋白和mRNA表达即有显著增高 (P <0 0 0 1) ;随着时间延长 ,LOX 1蛋白和mRNA表达量逐渐增加 ,至 2 4～ 36h达最高峰。缬沙坦可显著抑制AngII诱导的HUVECsLOX 1表达 ,使LOX 1表达接近于正常水平。结论AngII能明显增强HUVECs表达LOX 1,并呈浓度和时间依赖性 ,这可能是AngII促进动脉粥样硬化发生、发展的机制之一 ;此作用可被AT1拮抗剂缬沙坦阻断 ,从而产生可能的抗AS作用。
Objective To investigate the effects of valsartan, an angiotensin II (AngII) and angiotensin II receptor (AT1) antagonist, on the transcription and protein expression of the hemagglutinin-like oxidized low density lipoprotein receptor (LOX 1) gene in human umbilical vein endothelial cells Expression to further investigate the role and relationship of AngII and LOX 1 in atherosclerosis (AS), as well as the possible anti-AS effects of valsartan. Methods AngII (1 × 10 -5 ~1 × 10 -10 mol / L) was incubated with HUVECs for 24 hours, and AngII at a concentration of 1 × 10 -6 mol / L was incubated with HUVECs at different times (0, 6,12,2 4,36,48h), the expression of LOX 1 protein and mRNA were detected by enzyme-linked immunosorbent assay and semi-quantitative RT-PCR, and the effect of valsartan was observed. Results AngII increased the expression of LOX-1 protein and mRNA in HUVECs in a concentration-dependent manner. The expression of LOX-1 protein and mRNA in endothelial cells was significantly increased after treated with 10-6 mol / L AngII for 3 h (P <0.01) , LOX 1 protein and mRNA expression increased gradually, reaching the peak at 24 ~ 36h. Valsartan significantly inhibited LOX-1 expression induced by AngII in HUVECs, and the expression of LOX-1 was close to the normal level. Conclusion AngII can significantly enhance the expression of LOX-1 in HUVECs in a concentration- and time-dependent manner, which may be one of the mechanisms by which AngII promotes the development of atherosclerosis. This effect may be blocked by AT1 antagonist valsartan, resulting in Possible anti-AS effect.