TLR4/NF-κB信号转导通路介导吡格列酮在内脂素诱导内皮细胞炎症损伤过程中作用机制的探讨

TLR4/NF-κB signal pathway mediates pioglitazone protecting human vascular endothelial cells against visfantin-induced injury

目的：观察吡格列酮对内脂素诱导人脐静脉内皮细胞（HUVECs）炎症损伤过程中的影响，探讨吡格列酮改善内皮功能的信号转导机制。方法将HUVECs随机分组，给予不同浓度的内脂素进行诱导，运用蛋白印迹法（Western blotting）检测各组细胞Toll样受体4（TLR4）、细胞间黏附分子-1（ICAM-1）、核因子-κB（NF-κB）和NK-κB抑制蛋白α（IκB-α）的表达；再给予过氧化物酶体增殖物激活受体γ（PPARγ）激动剂吡格列酮，观察各组指标表达变化。结果与正常对照组相比，内脂素呈浓度依赖性地增加ICAM-1含量，下调IκB-α蛋白的表达，同时上调TLR4的表达，差异具有统计学意义（P＜0.05），且当内脂素浓度为1×10^-5mol/L时效果最显著。而吡格列酮呈浓度依赖性地抑制内脂素所诱导的上述效应，差异具有统计学意义（P＜0.05），当吡格列酮浓度为20μmol/L时效果最显著。结论吡格列酮对内脂素诱导的HUVECs炎症损伤有保护作用，其机制可能与抑制TLR4/NF-κB信号转导通路有关。

Objective To determine the effect of pioglitazone on visfantin-induced inflammatory injury in human vascular endothelial cells and investigate the underlying signal pathway of pioglitazone in improving endothelial functions. Methods Human umbilical vein endothelial cells （HUVECs） were treated by different concentrations of visfantin. Then Western blotting was used to detect the expression of Toll-like receptor4 （TLR4）, intercellular cell adhesion molecule-1 （ICAM-1）, nuclear factor-κB （NF-κB） and inhibitor of NK- κB-α （IκB-α）. Their expression levels were measured again after the cells were respectively exposed to the agonist of peroxisome proliferator activated receptor gamma （PPARγ）, pioglitazone. Results Compared with the control group, visfantin enhanced the expression of ICAM-1 in a dose-dependent manner, and also induced TLR4 up-regulation and IκB-α down-regulation （P〈0.05）, with visfantin at dose of 1×10^-5mol/L showing the strongest effect. However, pioglitazone inhibited the above effects of visfatin in a dose-dependent manner, with dose of 20 μmol/L having the maximal effect. Conclusion Pioglitazone exerts protective effect on visfantin-induced inflammatory injury in human vascular endothelial cells, which may be due to its blocking TLR4/NF-κB signal pathway.