高脂血症对内皮VCAM-1表达的影响及非诺贝特的血管保护作用

Impact of hyperlipidemia on VCAM-1 expression and cell adhesiveness of endothetium of rats

目的探讨血脂与炎性因子在动脉硬化早期对内皮功能的损伤机制。方法实验包括正常对照组(只喂基础饲料),另两组通过4周建立高脂血症模型,以后继续高脂喂养,其中非诺贝特治疗组在高脂喂养同时喂服非诺贝特40mg/(kg.d),而高脂血症组不予药物治疗,20周后检测3组的血脂、一氧化氮浓度及观察血管内皮VCAM-1的表达水平和细胞黏附密度。结果与正常对照组比较,高脂血症组NO水平较低、血管内皮上白细胞黏附增多、VCAM-1表达强度较强及范围较广。非诺贝特治疗组与高脂血症组比较,血NO水平提高、血管内皮VCAM-1表达水平和细胞黏附数目均较低(少)。结论高脂血症可抑制机体NO活性,并促进VCAM-1对血管内皮的损害,非诺贝特能有效地阻止动脉硬化的发生,该作用与一氧化氮水平提高、VCAM-1表达下调有关。

Objective To study the impact of hyperlipidemia and inflammation on endothelial lesion during the early stage of atheroscterosis. Methods This study included control（ basic chow）, hyperlipidemic and fenofibrate -treated groups（ high -fated diet）. Hyperlipidemic model was set up by feeding rats with 4 weeks of atherogenic diet, followed by 16 weeks of treatment in the fenofibrate -treated group [ fenofibrate 40 mg/（ kg · d） ] and without treatment in the hyperlipidemic group. Serum lipid level and NO concentration were measured. Expression of VCAM - 1 and cell adhesiveness on aortic endothelium was observed and analyzed by computer - aided system. Results Compared with the control group, hyperlipidemic rats showed lower level of NO and increase in leukocyte accumulation on the endothelial surface, as well as stronger and more extensive endothelial expression of VCAM - 1. In contrast, in fenofibrate - treated group, expression of VCAM - 1 as well as leukocyte adhesion significantly decreased which was associated with increased NO level. Conclusion NO activity is inhibited by hypertipidemia which facilitates endothelial impairment of VCAM - 1. Fenofibrate can prevent atherosclerosis by restoring NO concentration and down - regulating of VCAM - 1 expression.