氯沙坦保护ox-LDL诱导的内皮细胞损伤与ADMA的关系

Protective effect of losartan on injury induced by ox-LDL in endothelial cells and the relationship with asymmetric dimethylarginine

目的：探讨氯沙坦对氧化型低密度脂蛋白（ox-LDL）诱导的内皮细胞损伤的保护作用及其与内源性一氧化氮合酶抑制物非对称性二甲基精氨酸（ADMA）的关系。方法：用ox-LDL（100mg／L）孵育人脐静脉内皮细胞株HUVEC12 24h或用10^-8～10^-6mmol／L的氯沙坦预孵育HUVEC12 30min后再与ox-LDL共孵育24h，测定培养液中乳酸脱氢酶（LDH）活性、一氧化氮（NO）、肿瘤坏死因子-α（TNF-α）、ADMA含量和细胞内二甲基精氨酸二甲胺水解酶（DDAH）活性。结果ox-LDL孵育HUVEC12细胞24h后细胞培养液中LDH活性、TNF-α和ADMA含量明显增加（P〈0．05），同时NO含量下降和细胞DDAH酶活性受到抑制（P〈0．05）；氯沙坦（10^-8～10^-6mmoL／L）可显著减轻ox-LDL诱导的LDH活性、TNF-α和ADMA含量的增加以及NO含量的降低（P〈0．05），并呈浓度依赖性的增加DDAH活性（P〈0.05）。结论：氯沙坦对ox-LDL诱导的血管内皮细胞损伤具有保护作用，该作用可能与增加DDAH活性，降低ADMA浓度有关。

Objective To investigate the protective effect of losartan against on injury induced by ox-LDL in endothelial cells and the relationship with asymmetric dimethylarginine （ADMA）. Methods Endothelial injury was induced by incubation with ox-LDL 100 mg/L in cultured HUVECs for 24 h, and the levels of ADMA, lactate dehydrogenase （LDH）, nitric oxide （NO） and tumor necrosis factor-or （TNF-α） in the conditioned medium were measured. The activity of dimethylarginine dimethylaminohydrolase （DDAH） of cultured endothelial cells was also determined. Results Incubation of endothelial cells with ox-LDL 100 mg/L for 24 h induced a marked elevation of the levels of ADMA, LDH and TNF-α in the conditioned medium and a significant decrease in the activity of DDAH and the content of NO （P 〈0.05）. Pretreatment with losartan （ 10^-8 - 10^-6 mmoL/L） significantly inhibited the increased levels of ADMA, LDH and TNF-α, attenuated the decreased levels of NO and the decreased activity of DDAH induced by ox-LDL （P 〈0.05）. Conclusion Losartan may preserve ox-LDL-induced endothelial cell injury by increasing the DDAH activity and decreasing the ADMA level.