氯沙坦对小而密低密度脂蛋白致培养的人脐静脉内皮细胞损伤的保护作用

Protective Effect of Losartan on Human Umbilical Vein Endothelial Cells Injury Induced by Small Dense Low-density Lipoprotein in Culture

目的：观察氯沙坦对小而密低密度脂蛋白(sLDL)致人哜静脉内皮细胞(HUVECs)损伤的保护作用。方法：分离、鉴定 sLDL；用连续监测法测各组细胞乳酸脱氢酶(LDH)漏出量；用丙二醛试剂盒测定各组细胞上清中丙二醛(MDA)浓度；用硝酸还原酶法测定各组细胞分泌的一氧化氮(NO)量；用细胞-酶联免疫吸附法检测细胞膜上细胞间粘附分子-1(ICAM-1)蛋白表达量；反转录-多聚酶链反应(RT-PCR)法检测 ICAM-1mRNA 水平。结果：sLDL 使 HUVECs LDH 漏出增多、MDA 生成增多、NO 分泌减少、ICAM-1 表达增多,氯沙坦对此均有明显抑制作用,且呈剂量依赖性。结论：氯沙坦抑制 sLDL 致体外培养 HUVEcs 的损伤。

Objective:To observe the protective effect of losartan on human umbilical vein endothelial cell injury induced by sLDL in culture.Methods:Isolation,purification and identification of sLDL;the lactate dehydrogenase (LDH) leakage from cells were observed by continuous monitoring technique;the supernatant malondialdehyde (MDA)contents were assayed by MDA kit;the supernatant nitric oxide (NO)contents were estimated by nitrate reductase technique;The protein expression and their mRNA levels of intercellular cell adhesion molecule-1 were measured by enzyme linked immunosorbent assay(ELISA) and reverse transcription polymerase chain reaction (RT-PCR).Results:Comparison to the control group,sLDL increased the supernatant MDA,the lactate dehydrogenase leakage and decreased the nitric oxide releases.These effects induced by sLDL were all significantly inhibited by losartan the addition of sLDL upregulated protein and mRNA levels of ICAM-1 dramatically;losartan ameliorated the enhanced expression in a dose-dependent manner.Conclusion:sLDL may be involved in the initiation and progression of atherosclerosis by injuring the endothelial cells directly and causing endothelial dysfunction, losartan can protect against sLDL-inducing endothelial cell injury by blocking AT1 receptor suggesting that losartan may play a role in the prevention and treatment cardiovascular disease independently of blood pressure.