缬沙坦抑制非对称二甲基精氨酸诱导的内皮细胞LOX-1的表达

Valsartan Inhibited the Effect of Asymmetric Dimethylarginine Induced LOX-1 Expression in Human Umbilical Vein Endothelial Cells

目的研究缬沙坦对非对称二甲基精氨酸(ADMA)诱导的人脐静脉内皮细胞(HUVEC)凝集素样氧化型低密度脂蛋白受体1(LOX-1)mRNA和蛋白表达的影响,并探讨其机制。方法体外培养HUVEC,以不同浓度的缬沙坦和15μmol/L ADMA共同孵育24 h,DCFH-DA检测细胞内活性氧(ROS)生成量;RT-PCR测定NADPH氧化酶p22phox及LOX-1 mRNA的转录水平;酶联免疫吸附法检测细胞LOX-1蛋白的表达水平。结果与ADMA组相比,缬沙坦干预后细胞ROS水平显著下降(P<0.05),p22phox和LOX-1 mRNA转录水平及LOX-1蛋白的表达水平明显下调(P<0.05),并呈剂量依赖性。结论缬沙坦通过抑制p22phox的表达减少细胞内ROS水平,进而抑制ADMA诱导的内皮细胞LOX-1 mRNA转录和蛋白表达,这可能是其独立于降压作用的抗动脉粥样硬化作用的部分机制。

Aim To investigate the effects of valsartan on lectin-like oxidized low density lipoprotein receptor 1 （ LOX-1 ） expression induced by asymmetric dimethylarginine （ADMA） in cultured human umbilical vein endothelial ceils （HUVEC）. Methods 15 μmol/L ADMA was added into the cultured HUVEC for 24 h, intracellular reactive oxygen species （ROS） generation was measured by DCFH-DA. NADPH p22phox subunit and LOX-1 mRNA transcription were detected by quantitative competitive reverse transcription-polymerase chain reaction （RT-PCR）. LOX-1 protein ex- pression was detected by cell enzyme linked immunosorbent as＇say （ELISA）. Results Valsartan significantly decreased intracellular ROS generation, inhibited the transcription of p22phox, LOX-1 mRNA and LOX-1 protein expression compared with ADMA group （P 〈 0. 05 ）, and this effect was in a dose-dependent manner. Conclusions Valsartan inhibited expression of LOX-1 induced by ADMA, involving in inhibiting the expression of p22phox through decreasing intracellular ROS generation. This may be part of the mechanism of its anti-atherosclerotic effect independent of anti-hypertensive effect.