罗格列酮对同型半胱氨酸硫内酯所致内皮细胞损伤的保护作用与PPARγ介导的抗氧化相关  

Effects of Rosiglitazone Against Homocysteine Thiolactone Induced the Injuries of Endothelial Cell Related to PPARγ-mediared Antioxidant Effects

作　　者：杨旭红[1] 李鹏[2] 戴文[1] 熊小明[1] 涂江华[1] 吴树金[1] 刘立英[1] 

机构地区：[1]中南大学药学院药理学教研室,湖南省长沙市410078 [2]新乡医学院临床药理学教研室,河南省新乡市453003

出　　处：《中国动脉硬化杂志》2015年第6期549-555,共7页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(81270395);湖南省卫生厅课题(B20082023);长沙市科技局课题(K0802085231)

摘　　要：目的探讨罗格列酮对同型半胱氨酸硫内酯(HTL)所致血管内皮细胞损伤的保护作用及其机制。方法在培养的人脐静脉内皮细胞(HUVEC),用HTL与HUVEC共孵,用罗格列酮、卡托普利、夹竹桃麻素、过氧化体增殖物激活型受体γ(PPARγ)拮抗剂GW9662、核因子κB(NF-κB)信号传导通路抑制剂吡咯二硫代氨基甲酸乙酯(PDTC)进行预干预,MTT比色法检测细胞活力,逆转录聚合酶链反应检测PPARγm RNA的表达,荧光探针DCFADA检测细胞内活性氧簇(ROS),免疫荧光检测法测定NF-κB P65,酶标法检测可溶性细胞间黏附分子1(s ICAM-1)。结果 HTL与HUVEC共孵育24 h,明显降低内皮细胞活力,增加细胞内ROS水平和NF-κB的活化,升高细胞培养液中s ICAM-1的浓度(P<0.01)。罗格列酮(0.001、0.01、0.1 mmol/L)能浓度依赖性地拮抗HTL所致的内皮细胞活力降低,抑制细胞内ROS水平的增加和NF-κB的活化,降低细胞培养液中s ICAM-1的浓度,与单独HTL损伤组比较,差异有显著性(P<0.05或P<0.01)。上述保护作用可被选择性的PPARγ拮抗剂GW9662所拮抗。夹竹桃麻素、卡托普利、PDTC对HTL引起的上述指标改变也有明显改善作用。结论罗格列酮对HTL所致的HUVEC损伤有显著保护作用,其机制可能与PPARγ介导的氧化应激反应的抑制有关。Aim To explore whether rosiglitazone,exerts beneficial effects on injuries of endothelial cells induced by homocysteine thiolactone( HTL) and to investigate the potential mechanisms. Methods The cultured human umbilical vein endothelial cells( HUVEC) were respectively preincubated with rosiglitazone,and other interference factors including apocynin,captopril,pyrollidine dithiocarbamate( PDTC) and antagonist of peroxisome proliferator activated receptor-γ( PPARγ) GW9662 for 1 hour,and then sequentially incubated with HTL( 1 mmol / L) for 24 hours. The cell viability,the level of reactive oxygen species( ROS),the activity of nuclear factor-κB( NF-κB),the concentration of soluble intercellular adhesion molecule-1( s ICAM-1),the expression of PPARγ m RNA were examined. Results HTL decreased obviously the HUVEC viability,enhanced the level of ROS and activation of NF-κB,the concentration of s ICAM-1 and down-regulated the expression of PPARγ m RNA. Preincubation of HUVEC with rosiglitazone( 0. 001,0. 01,0. 1mmol / L),apocynin( 0. 1 mmol / L),captopril( 0. 03 mmol / L),PDTC( 0. 1 mmol / L) for 1 hour reversed these effects induced by HTL,compared with alone HTL group( P < 0. 05 or P < 0. 01). Further,co-incubation with PPARγ antagonist GW9662( 0. 01 mmol / L),abolished the protective effects of rosiglitazone on HTL-treated cells. Conclusions Rosiglitazone has protective effects against injuries of endothelial cells induced by HTL,which is related to PPARγ-mediared suppression of oxidative stress.

关 键 词：罗格列酮 同型半胱氨酸硫内酯 过氧化体增殖物激活型受体Γ 内皮细胞 氧化应激 

分 类 号：R96[医药卫生—药理学]