Ox-LDL通过LOX-1双重调节血管内皮细胞炎性分子的表达  

Dual roles of oxidized LDL in modulating expression of inflammatory molecules in HUVECs

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

机构地区：[1]中山大学公共卫生学院,广东广州510080

出　　处：《中国病理生理杂志》2007年第8期1464-1469,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学杰出青年基金资助项目(No.30025037)

摘　　要：目的:探讨LOX-1/PPARγ信号途径对Ox-LDL诱导血管内皮细胞炎性分子表达的影响。方法:用聚肌苷酸[poly(I)]、卡拉胶(carrageenan)、15脱氧前列腺素J2(15d-PGJ2)以及Ox-LDL与脐静脉内皮细胞(HUVECs)作用,用realtime RT-PCR测定LOX-1和PPARγ、RT-PCR测定ICAM-1和E-selectin的mRNA的表达;用Western blotting测定PPARγ、ICAM-1和E-selectin蛋白的表达。结果:Ox-LDL可以显著上调PPARγmRNA和蛋白的表达(P<0.01),并呈明显的剂量效应关系,poly(I)和carrageenan可以显著抑制Ox-LDL对PPARγ的上调作用。在HUVECs中预先单独加入15 d-PGJ2或与polyinosonic acid一起预先作用,然后再加入Ox-LDL。15d-PGJ2可以降低Ox-LDL诱导的ICAM-1、E-selectin和LOX-1的表达;PPARγ的受体激动剂与LOX-1的受体阻断剂联合作用,其降低ICAM-1和E-selectin表达的作用比单独使用15d-PGJ2或polyinosonicacid要显著。结论:Ox-LDL一方面引起血管内皮细胞的炎性损伤,另一方面启动细胞抗炎作用,在炎性反应过程中呈现双重的调节作用。AIM ： To determine the role of LOX - 1/PPAR pathway in regulating expression of adhesion molecules elicited by oxidizing low density lipoprotein（ Ox -LDL） through Lectin -like oxidized low -density lipoprotein receptor - 1 （ LOX - 1 ） in human umbilical vein endothelial cells （HUVECs）. METHODS： HUVECs were incubated with Ox - LDL, poly（ I ） , carrageenan or 15 - deoxy - △^ 12.14 - prostaglanding J2 （ 15d - PGJ2 ）. PPAR mRNA and protein were examined by real time RT - PCR and Western blotting. ICAM - 1 and E - selectin were detected by RT - PCR and Western blotting respectively. RESULTS： Ox -LDL increased PPAR expression in HUVECs, which was inhibited by pretreatment of HUVECs with LOX - 1 blockers. Preincubation of HUVECs with 15d - PGJ2 attenuated the expression of intercellular adhesion molecule - 1 （ ICAM - 1 ） and E - selectin in response to Ox - LDL. Upregulation of ICAM - 1 and E - selectin mediated by Ox - LDL were suppressed more significantly by the combination of 15d - PGJ2 and polyinosonic acid as compared to either 15d - PGJ2 or polyinosonic acid alone. CONCLUSION： The results indicate that Ox - LDL exerts a biphasic effects on inflammatory response. It evokes harmful effects by inflammatory injury on one side and protective effects by triggering the LOX - 1/PPAR signaling pathway on the other hand.

关 键 词：脂蛋白类 LDL 受体 脂蛋白 血管内皮细胞 过氧化酶体增殖物激活受体 胞间粘附分子1 

分 类 号：R363[医药卫生—病理学]