罗格列酮对高糖诱导的血管内皮细胞炎症的抑制作用

Rosiglitazone Prevents High Glucose-Induced Inflammation in Vascular Endothelial Cells

目的阐明罗格列酮对糖尿病血管并发症保护作用的分子机制。方法用凝胶迁移分析和免疫荧光法测定不同浓度罗格列酮干预前后高糖诱导的血管内皮细胞核因子κB激活和血管细胞黏附分子1表达的改变。结果 25mmol/LD-葡萄糖刺激30min可诱导细胞核因子κB向核内迁移(与基础水平相比,P<0.001);5、25μmol/L罗格列酮以剂量依赖的方式抑制了D-葡萄糖诱导这种效应,抑制率分别为25.17%(P=0.001)和51.79%(P<0.001)。罗格列酮还抑制了D-葡萄糖诱导的血管细胞黏附分子1高表达。结论罗格列酮通过抑制血管内皮细胞炎症起到直接保护血管作用,可能是其延缓和改善糖尿病血管并发症的机制之一。

Aim To clarify the molecular mechanism of protective effect of rosiglitazone on vascular complication of diabetes. Methods Human umbilical vascular endothelial cells （HUVEC） were exposed to medium or high glucose in the presence or absence of different doses of rosiglitazone. Nuclear translocation of nuclear factor-κB（NF-κB） was measured using the electrophoretic mobility shift assay and immunofluorescence. Expression of vascular cell adhesion molecule-1（VCAM-1） was determined by immunofluorescence. Results 25 mmol/L D-glucose significantly induced nuclear translocation of NF-κB in HUVEC （P〈0.001 vs that of basal level）,which was prevented by 5 and 25 μmol/L of rosiglitazone in a dose-dependent manner. The suppression rate was 25.17% （P=0.001） and 51.79% （P〈0.001）. Rosiglitazone also prevented the increased expression of VCAM-1 induced by D-glucose. Conclusion Rosiglitazone directly protects vascular function via inhibition of inflammation in vascular endothelial cells and that is perhaps one of the mechanisms of rosiglitazone improving vascular complication of diabetes.