【摘要】 背景:血凝素样氧化型低密度脂蛋白受体1作为氧化型低密度脂蛋白的特异性受体,参与血管性炎症和粥样斑块的发生发展过程。近年发现他汀类药物调脂外抗炎症作用可能是其抗动脉粥样硬化机制之一。目的:验证氟伐他汀对氧化低密度脂蛋白刺激下人脐静脉内皮细胞氧化型低密度脂蛋白受体1表达的影响。设计、时间及地点:对比观察,实验于2006-08/2007-05在中南大学湘雅医学院附属第二医院医学实验中心完成。材料:人脐静脉内皮细胞株购自美国ATCC公司。氟伐他汀原粉购自北京诺华制药有限公司。方法:培养人脐静脉内皮细胞株,按以下方法处理:①用氧化型低密度脂蛋白刺激细胞(终浓度分别为25,50,100mg/L)。②以氧化型低密度脂蛋白受体1中和抗体干预后,再加入50mg/L氧化型低密度脂蛋白干预。③以核因子кB抑制剂PDTC干预后,再加入50mg/L氧化型低密度脂蛋白干预。④以不同浓度(0.01,0.1,1μmol/L)氟伐他汀干预后,再加入50mg/L氧化型低密度脂蛋白干预。⑤空白组为对照。主要观察指标:采用反转录-聚合酶链反应技术检测氧化型低密度脂蛋白受体1mRNA的表达水平。结果:在氧化型低密度脂蛋白各剂量组(25,50,100mg/L)均可上调人脐静脉内皮细胞氧化型低密度脂蛋白受体1mRNA的表达,在25～50mg/L剂量范围内呈显著的剂量-效应关系(P<0.01)。预先分别给予氧化型低密度脂蛋白受体1中和抗体和核因子кB抑制剂PDTC干预,氧化型低密度脂蛋白受体1mRNA的表达均下调。予以不同浓度氟伐他汀干预呈浓度依赖性降低氧化型低密度脂蛋白刺激的人脐静脉内皮细胞氧化型低密度脂蛋白受体1mRNA的表达。结论:氟伐他汀呈浓度依赖性降低氧化型低密度脂蛋白刺激下人脐静脉内皮细胞氧化型低密度脂蛋白受体1的表达,可能与其抑制核因子кB的表达,减轻内皮细胞炎症反应,从而发挥其独立于降脂外的抗炎效应。更多还原

【Abstract】 BACKGROUND:Oxidized low-density lipoprotein(ox-LDL) is recognized as the essential condition for atherosclerosis.As the ox-LDL-specific receptor,oxidized low-density lipoprotein receptor-1(LOX-1) involved in vascular inflammation and plaques develop-ment of the process.OBJECTIVE:To investigate the effect of fluvastatin on the expression of LOX-1 in human umbilical vein endothelial cells(HUVECs) induced by ox-LDL.DESIGN,TIME AND SETTING:The comparative observation was completed in the Medical Center of Second Xiangya Hospital,Central South University between August 2006 and May 2007.MATERIALS:Human umbilical vein endothelial cell line was purchased from the America ATCC Company.Fluvastatin original powder was supplied by Beijing Novartis Pharmaceutical Co.,Ltd.METHODS:HUVECs were incubated with:①Stimulation by ox-LDL with end concentration of 25,50,100 mg/L.②LOX-1 neutralizing antibody,and interfered with 50 mg/L ox-LDL.③Interfered with nuclear factor-кB(NF-кB) blockers pyrrolidine dithiocarbamate(PDTC),followed by 50 mg/L ox-LDL intervention.④Fluvastatin with concentration of 0.01,0.1,1 μmol/L were used to interfere the cells,followed by 50 mg/L ox-LDL intervention.⑤There was an blank group as the control.MAIN OUTCOME MEASURES:The expression of LOX-1 mRNA level was detected by RT-PCR.RESULTS:The levels of mRNA of LOX-1 were increased after cells had beenwere incubated with different concertrations of ox-LDL,when compared with the control group.Within the dosage range of 25 to 50 mg/L,the above-mentioned indexes significantly changed in a concentration-dependent manner(P < 0.01).Those HUVECs were pretreated with LOX-1 neutralizing antibody or PDTC decreased the mRNA expression of LOX-1 mRNA induced by ox-LDL.Pretreatment of HUVECs with fluvastatin in different concentrations for 24 hours could decrease the expression of mRNA of LOX-1 induced by ox-LDL in a dose-dependent manner.CONCLUSION:Fluvastatin decreases LOX-1expression on HUVECs induced by ox-LDL in a dose-dependent manner.This may be associated with the inhibition of fluvastatin on the NF-κB and the inflammation of endothelial cells,which may be one of the mechanisms of anti-inflammation exception of lipid-lowering capacity.更多还原