摘要
目的通过检测人脐静脉内皮细胞的氧化应激、细胞黏附分子和炎症相关信号分子表达,探讨阿魏酸在肿瘤坏死因子α(TNF-α)诱导的血管内皮损伤中的保护作用和机制。方法以人脐静脉内皮细胞为研究模型,给予阿魏酸预处理,在基础或者TNF-α刺激条件下,蛋白质免疫印记法检测细胞间黏附分子1(ICAM-1)、血管细胞黏附分子1(VCAM-1)表达和炎症相关细胞信号分子;MTT法检测内皮细胞活性;Hoechst 33342细胞核染色检测细胞凋亡比率;以DHE染色检测氧自由基(ROS)生成;单核细胞和血管内皮细胞黏附实验检测血管内皮细胞的黏附功能;以蛋白质免疫印记法和细胞免疫荧光实验检测核因子κB(NF-κB)的活化。结果 TNF-α可以明显增加血管内皮细胞氧自由基生成及ICAM-1和VCAM-1的表达,并且可以明显激活NF-κB,促进其核转位。阿魏酸可以明显抑制TNF-α诱导的血管内皮细胞氧自由基生成及ICAM-1和VCAM-1表达升高,抑制NF-κB活化和核转位。结论阿魏酸可以通过抑制NF-κB信号途径减轻TNF-α导致的血管内皮细胞氧自由基增高、黏附分子表达,抑制炎性因子导致的细胞损伤。
Aim To investigate the effect and mechanism of ferulic acid (FA) on the expression of adhesion molecules and oxidative stress in tumor necrosis factor-α (TNF-α)treated human umbilical vein endothelial cells (HU- VEC). Methods An endothelial cell model of adhesion function damage was established by administration of TNF-α. The level of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 ( VCAM-1) was determined by Western blot . HUVEC viability and apoptosis were detected by MTT and Hoechst 33342 staining. Reactive oxygen species (ROS) production was measured by DHE staining. Adhesion assay of monocyte and HUVEC was used to detect endothelial cell adhesive function. Nuclear factor-kβ (NF-kβ) activation was detected by Western blot and immu- nofiuorescence staining. Results The TNF-ct treatment caused a significant increase of ROS generation and the expression of ICAM-1 and VCAM-1 in HUVEC, which was associated with a dramatic augmentation in phosphorylation of I- kβ and relocation of NF-kβ into the nuclei. However, TNF-α-induced ROS generation, ICAM-1 and VCAM-1 upregnlation and NF-kβ relocation could be attenuated by pretreat ment of fernlic acid. Conclusion Ferulic acid could sup- press TNF-α-induced adhesion molecule expression by blocking NF-kβ signal and inhibiting ROS generation in HUVECs, suggesting that fernlic acid could be a novel drug candidate for the prevention and treatment of atherosclerosis.
出处
《中国动脉硬化杂志》
CAS
CSCD
北大核心
2013年第5期385-390,共6页
Chinese Journal of Arteriosclerosis
基金
国家自然科学基金青年基金项目(81200221)
国家人力资源和社会保障部留学回国人员科研启动基金
关键词
阿魏酸
抗氧化剂
内皮细胞
肿瘤坏死因子Α
细胞黏附分子
Ferulic Acid
Antioxidants
Endothelial Cell
Tumor Necrosis Factor-a
Cell Adhesive Molecule