罗格列酮对TNF-α刺激人脐静脉内皮细胞CF6表达的影响

Effect of rosiglitazone on tumor necrosis factor-α-induced nuclear factor-κB and coupling factor 6 expressions in human umbilical vein endothelial cells

目的研究噻唑烷二酮类药物罗格列酮(ROS)对肿瘤坏死因子α(TNF-α)诱导的体外培养人脐静脉血管内皮细胞(HUVEC)核因子-κB(NF-κB)激活与线粒体偶联因子6(CF6)表达的影响。方法体外培养的第3～5代HUVEC用于实验。采用RIA检测培养基中CF6的含量,用免疫组织化学分析检测细胞NF-κB亚单位p65的表达程度。结果TNF-α能有效激活NF-κB并诱导HUVEC表达CF6增加;ROS干预能抑制NF-κB激活并减轻TNF-α诱导的HUVEC之CF6表达。结论TNF-α通过激活NF-κB使CF6表达增加;ROS可抑制TNF-α对NF-κB激活,进而抑制NF-κB对CF6的表达上调,这可能是噻唑烷二酮类药物抗高血压的机制之一。

Objective To investigate the effect of rosiglitazone on the expression of nuclear factor-κB （NF-κB） and coupling factor 6 （CF6） induced by tumor necrosis factor-α （TNF-α） in cultured human umbilical vein endothelial cells （HUVEC）. Methods Cultured HUVEC of passage 3-5 were stimulated with TNF-α and then cultured in the presence of rosiglitazone. The expression of CF6 and NF-KB subunit p65 were evaluated by immuncytochemistical method. Results Pretreatment of HUVECs with rosiglitazone inhibited TNF-α-induced expression of CF6 in a dose-dependent manner. The activation of CF6 stimulated by TNF-α was suppressed by ROS in a dose-dependent manner. Conclusion TNF-α-induced enhancement of the gene expression and release of CF6 is mediated by activation of NF-κB signaling pathway. ROS can inhibit the activation of IKK, block NF-κB signaling pathway and inhibit the expression of CF6, which may be the mechanism underlying the action of TZDs on hypertension.