摘要
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 evaluate the effect of angiotensin II (AngII) and a specific type 1 angiotensin II receptor (AT1) antagonist, valsartan, on lectin like oxidized low density lipoprotein recpter 1 (LOX 1) mRNA and protein expression in cultured human umbilical vein endothlial cells(HUVECs) Methods Several groups of cultured HUVECs were incubated with AngII of 1×10 -5 ～1×10 -10 mol/L for 24 hours or with 1×10 -6 mol/L AngII for various times up to 48 hours In other groups of HUVECs, valsartan(1×10 -6 mol/L)was added to the culture medium half an hour before cells were incubated with 1×10 -6 mol/L AngII for 24 hours Then HUVECs LOX 1 protein expression was measured by endothlial cell enzyme linked immunosorbent assay(ELISA), and LOX 1 mRNA expression was detected by quantitative competitive reverse transcription polymerase chain reaction (RT PCR) Results AngII markedly induced the increase of HUVECs LOX 1 protein and mRNA expression The increase in LOX 1 expression was dependent on AngII concentration (1×10 -5 ～1×10 -10 mol/L) After treatment with 1×10 -6 mol/L AngII for 3 hours, HUVECs LOX 1 expression was elevated ( P <0 05) in HUVECs, reaching its maxium at 24～36 hours The effect of AngII were blocked by pretreatment of HUVECs with 1×10 -6 mol/L valsartan Conclusion AngII concentration dependently and time dependently upregulated Lox 1 expression in HUVECs AT1 blocker, valsartan, could block it These effects of AngII may contribute to the pathogenesis of atherosclerosis, and valsartan may produce anti atherosclerosis
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2002年第10期630-633,共4页
Chinese Journal of Cardiology
