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

发布时间：2018-06-29 23:53

本文选题：罗格列酮 + 同型半胱氨酸硫内酯　；参考：《中国动脉硬化杂志》2015年06期

【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(P0.01)。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(P0.05或P0.01)。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。
[Abstract]:Objective to investigate the protective effect of rosiglitazone on vascular endothelial cell injury induced by homocysteine thiolactone (HTL) and its mechanism. Methods cultured human umbilical vein endothelial cells (HUVEC) were incubated with HTL and HUVEC. GW9662, an antagonist of peroxisome proliferator activated receptor 纬 (PPAR 纬), and pyrrorodithiocarbamate ethyl ester (PDTC), a signal transduction pathway inhibitor of nuclear factor- 魏 B (NF- 魏 B), were used to detect cell viability by MTT colorimetry, and the expression of PPAR 纬 mRNA by reverse transcriptase polymerase chain reaction (RT-PCR). Intracellular reactive oxygen species (Ros), NF- 魏 B P65 and soluble intercellular adhesion molecule-1 (sICAM-1) were detected by fluorescence probe DCFADA and immunofluorescence respectively. Results after incubation with HUVEC for 24 h, HTL significantly decreased the activity of endothelial cells, increased the level of Ros and the activation of NF- 魏 B, and increased the concentration of sICAM-1 in the culture medium (P0.01). Rosiglitazone (0.001) could antagonize the decrease of endothelial cell viability induced by HTL in a concentration-dependent manner, inhibit the increase of intracellular Ros level and the activation of NF- 魏 B, and decrease the concentration of sICAM-1 in cell culture medium. The difference was significant (P0.05 or P0.01). These protective effects can be antagonized by selective PPAR 纬 antagonist GW 9662. The changes of the above indexes induced by HTL were also significantly improved by diaphanol and captopril PDTC. Conclusion rosiglitazone has a significant protective effect on HTL-induced HUVEC injury, and its mechanism may be related to the inhibition of PPAR 纬 -mediated oxidative stress.
【作者单位】：中南大学药学院药理学教研室;新乡医学院临床药理学教研室;
【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)
【分类号】：R96

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