普罗布考对氧化修饰低密度脂蛋白诱导的人内皮细胞TOLL样受体4表达及单核内皮细胞黏附功能的影响  

Effect of probucol on human endothelial cell Toll-like receptor 4 expression induced by oxidized low density lipoprotein and adhesion function of monocytes

作　　者：杨清武[1] 牟玲[2] 王琳[1] 王景周[1] 高东[1] 周红杰[1] 向静[1] 

机构地区：[1]解放军第三军医大学大坪医院神经内科,重庆市400042 [2]解放军第三军医大学预防医学系毒理教研室,重庆市400038

出　　处：《中国临床康复》2005年第7期75-77,i004,共4页Chinese Journal of Clinical Rehabilitation

基　　金：国家自然科学基金资助项目(30170968)~~

摘　　要：目的:探讨普罗布考对氧化修饰低密度脂蛋白(oxidizedlowdensitylipoprotein,ox-LDL)诱导的人脐静脉内皮细胞TLR4表达及其黏附功能的影响,为进一步研究普罗布考抗动脉粥样硬化的机制,发现抗动脉粥样硬化形成的新靶点提供理论依据。方法:应用RT-PCR,WesternBlot技术检测了普罗布考对ox-LDL诱导的细胞TOLL样受体4(toll-likereceptor4,TLR4)表达的影响,同时用孟加拉玫瑰红活细胞染色法观察不同浓度普罗布考对ox-LDL诱导的人脐静脉内皮细胞(humanumbilicalveinendothelialcells,HUVECs)对单核细胞黏附的影响,并利用相关性检验分析两者间的相关性。结果:ox-LDL能明显上调HUVECsTLR4的表达,并呈一定的剂量依赖性(t=3.04～12.52,P<0.01)。普罗布考呈浓度依赖方式抑制ox-LDL诱导HUVECsTLR4表达,同时也能明显抑制ox-LDL诱导的HUVECs对单核细胞黏附(t=5.30,19.23,P<0.01)。相关性分析显示两者间有明显的正相关性(r=0.996,P<0.01)。结论:普罗布考除具有调脂作用外,尚可通过抑制ox-LDL诱导的内皮细胞TLR4受体的表达和抑制单核细胞与内皮细胞黏附聚集,发挥抗炎作用;TLR4可能成为防治动脉粥样硬化的新靶点。AIM: To investigate the influence of probucol on Toll-like receptor 4 (TLR4) expression and adhesion function of human umbilical vein endothelial cells (HUVECs) induced by oxidized low density lipoprotein (ox-LDL), so as to provide theoretical evidence for further study of the anti-atherosclerosis mechanism of probucol and find out the new target for prevention and treatment of atherosclerosis. METHODS: The effect of probucol on TLR4 expression induced by ox-LDL was detected with RT-PCT and Western blot analysis, and effect of probucol of different concentrations on HUVECs adhesion to monocytes was observed by using rose bengal staining. The relation between the changes of TLR4 expression and cell adhesion was assayed with correlation analysis. RESULTS: Ox-LDL could obviously up-regulate TLR4 expression in HUVECs with concentration dependent manner (t=3.04 to 12.52, P< 0.01). Probucol could inhibit significantly the expression of TLR4 in HUVECs and monocytes adhesion to endothelial cells with concentration dependent manner (t=5.30,19.23, P< 0.01). Correlation analysis revealed that the changes of TLR4 expression positively were correlated with the changes of cell adhesion(r=0.996, P< 0.01). CONCLUSION: Probucol cannot only regulate lipid, but also has the action of anti-inflammation through inhibiting TLR4 expression and monocytes adhesion induced by ox-LDL. TLR4 may be a new target for the prevention and treatment of atherosclerosis.

关 键 词：内皮 血管/细胞学 普罗布可/药理学:脐静脉/细胞学 细胞黏附/药物作用 

分 类 号：R54[医药卫生—心血管疾病]