氧化低密度脂蛋白通过血凝素样氧化低密度脂蛋白受体1诱导血管内皮细胞粘附分子的表达  

Effects of LOX-1 on expression of adhesion molecules induced by ox-LDL in HUVECs

作　　者：朱惠莲[1] 夏敏[1] 侯孟君[1] 唐志红[1] 郑佩英[1] 凌文华[1] 

机构地区：[1]中山大学公共卫生学院,广州510080

出　　处：《中华心血管病杂志》2005年第8期743-747,共5页Chinese Journal of Cardiology

基　　金：国家自然科学杰出青年基金资助项目(30025037)

摘　　要：目的探讨血凝素样氧化低密度脂蛋白受体1(LOX-1)在氧化低密度脂蛋白(ox-LDL)诱导血管内皮细胞粘附分子表达中的作用.方法用不同浓度ox-LDL培养人脐静脉内皮细胞(HUVECs),用Rrealtime RT-PCR测定LOX-1 mRNA的表达;RT-PCR测定细胞间粘附分子1(ICAM-1)、血管细胞粘附分子1(VCAM-1)以及E选择素的mRNA表达;用Western blot测定LOX-1、ICAM-1、VCAM-1以及E选择素蛋白的表达,观察ox-LDL对血管内皮细胞粘附分子表达的影响.HUVECs预先用聚肌苷酸[poly(I)]和爱兰苔胶处理,再用ox-LDL培养,再分别测定上述粘附分子的表达水平,比较加入LOX-1阻断剂前后粘附分子表达的变化.结果 ox-LDL各剂量组皆可上调LOX-1、ICAM-1、E选择素的mRNA和蛋白表达(P<0.01),在10～50 μg/ml剂量范围内呈现明显的剂量-效应关系(P<0.01),但ox-LDL对VCAM-1的表达没影响. HUVECs预先与250 μg/ml 的poly(I)或爱兰苔胶作用2 h,然后加入50 μg/ml的ox-LDL作用24 h.poly(I)和爱兰苔胶都能抑制ox-LDL诱导的LOX-1、ICAM-1和E选择素的mRNA和蛋白表达水平,与未阻断组相比,差异皆有统计学意义(P<0.01).结论 ox-LDL可以上调血管内皮细胞粘附分子的表达,LOX-1受体阻断剂可以部分阻断ox-LDL的上调作用,ox-LDL诱导血管内皮细胞粘附分子的表过是通过LOX-1介导的.Objective To investigate the effects of oxidized low-density lipoprotein receptor 1 （LOX-1） on secretion of adhesive molecules mediated by ox-LDL in human umbilical endothelial cells （HUVECs）. Methods HUVECs with different concentration of ox-LDL （0, 10, 20, 50, 100 μg/ml） were incubated for 24 h, or HUVECs were pretreated with 250 μg/ml poly （Ⅰ） or 250 μg/ml carrageenan for 2 h and then incubated with 50 μg/ml ox-LDL for another 24 h. Expression of LOX-1 was determined by realtime RT-PCR and Western blot. mRNA and protein of ICAM-1, VCAM-1 and E-selectin were examined by RT-PCR and Western blot respectively. Results Incubation of HUVECs with ox-LDL （ 10-100 μg/ml ） enhanced the expressions of LOX-1, ICAM-1 and E-selectin in a concentration-dependent manner （P 〈 0.01 ）. On the contrary, ox-LDL did not affect the expression of VCAM-1 by HUVECs. The expression of LOX-1, ICAM-1 and E-selectin induced by ox-LDL were reduced in HUVECs pretreated with 250 μg/ml poly （I） or 250 μg/ml carrageenan for 2 h and then incubated with 50 μg/ml ox-LDL for 24 h . This showed that both poly （Ⅰ） and carrageenan obviously decreased the expression of LOX-1, ICAM-1 and E- selectin induced by ox-LDL. Conclusion ox-LDL may upregulate the expression of LOX-1, ICAM-1 and E-selectin, and LOX-1 blocker may partly inhibit this upregulation. The results suggest that the expression of inflammatory molecules induced by ox-LDL in HUVECs is mediated by LOX-1.

关 键 词：动脉硬化 脂蛋白类 LDL 内皮 血管 血凝素样氧化低密度脂蛋白受体1 血凝素样氧化低密度脂蛋白受体 血管内皮细胞粘附分子 OX-LDL诱导 WESTERNBLOT 

分 类 号：R543.3[医药卫生—心血管疾病]