氧化型脂蛋白(a)对人脐静脉血管内皮细胞P选择素表达的影响

Oxidized lipoprotein(a) enhanced the expression of P-selectin in cultured human umbilical vein endothelial cells

目的 探讨氧化修饰的脂蛋白 (a) [ox Lp(a) ]能否诱导人脐静脉内皮细胞表达P选择素 ,以阐明其在动脉粥样硬化发生中的作用。方法 在内皮细胞培养基中分别加入天然脂蛋白 (a)[n Lp(a) ]与ox Lp(a)及天然与氧化的低密度脂蛋白 (n LDL、ox LDL)。用细胞酶联免疫检测P选择素蛋白的表达 ,用单核细胞黏附率试验检测单核细胞黏附 ,并用Northern杂交检测P选择素mRNA的表达。结果 ox Lp(a)呈剂量依赖性增加内皮细胞P选择素蛋白表达 ,10nmol/L及 2 0nmol/Lox Lp(a)分别使P选择素表达明显增加到 (145± 10 ) %及 (2 0 2± 2 2 ) %。同时观察到ox Lp(a)促使单核细胞黏附率增加 ,并且黏附率与加入的ox Lp(a)浓度呈正相关。四种脂蛋白的作用进行比较显示ox Lp(a)的作用最强 ,10nmol/Ln LDL、n Lp(a)、ox LDL、ox Lp(a)分别使P选择素表达增加到 (10 5± 7) %、(12 7± 9) %、(176± 19) %、(2 45± 2 2 ) %。Northernblot结果显示ox Lp(a)能促使P选择素mRNA表达明显增加。结论 ox Lp(a)能诱导内皮细胞表达P选择素增强 ,这可能与脂蛋白 (a)致动脉粥样硬化作用机制有关。

Objective To investigate the effects of oxidized lipoprotein(a) on the expression of P selectin in cultured human umbilical endothelial cells (HUVECs).Methods Native Lp(a), native low density lipoprotein(n LDL),oxidized LDL (ox LDL) and ox Lp(a) were incubated with HUVECs.Cell ELISA was used to detect the expression of P selectin protein. Monocyte adhesion assay was used to detect the P selectin mRNA expression. Results ox Lp(a) dramatically enhanced the levels of P selectin in a dose dependent manner, increasing P selectin expression in HUVECs by (145±10)% at 10 nmol/L and (202±22)% at 20 nmol/L. In addition, treatment of 10 nmol/L of ox Lp(a)for 2 h could significantly increase the amount of monocyte adherence to endothelial cells. Moreover,ox Lp(a) was the most potent stimulus for P seclectin expression, 10nmol/L n LDL,n Lp(a), ox LDL and ox Lp(a) increased the P selectin expression to (105±7)%, (127±9)%, (176±19)%,(245±22)%, respectively. Furthermore,Northern blot analysis demonstrated that the amount of P selectin mRNA was increased after treatment with 10 nmol/L of ox Lp(a) for 24 h. Conclusion ox Lp(a) can induce P selectin expression in HUVECs, which may thereby influence the pathogenesis of athersclerosis.