非诺贝特对高脂血症大鼠NO及血管内皮细胞粘附分子-1表达的影响

Impact of fenofibrate on No and endothelial VCAM-1 expression in hyperlipidemic rats

目的探讨血脂与炎性因子对内皮功能的损伤机制。方法实验包括正常对照组(基础饲料喂养),高脂血症组(高脂喂养)和高脂血症非诺贝特治疗组(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-1·d-1)而高脂血症组不予药物治疗,20周后检测3组的血脂、NO浓度及观察血管内皮血管细胞粘附分子-1(VCAM-1)的表达水平和细胞粘附密度。结果与正常对照组比较,高脂血症组NO水平较低、血管内皮上白细胞粘附增多、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表达水平和细胞粘附数目均较低(少)。结论NO减少及炎症因素的介入参与了血管损害机制,非诺贝特能有效地阻止动脉硬化的发生,该作用与NO水平提高、VCAM-1表达下调有关。

Objective To investigate the mechanism of hyperlipidemia- and imflammation-induced functional impairment of the endothelium. Methods The experiment was conducted using 3 groups of rats fed for 20 weeks with standard chow （control group）, high-fat diet and high-fat diet with daily fenofibrate treatment （10 mg/kg, starting since the fifth week）, respectively. Afer 4 and 20 weeks of feeding, respectively, serum lipid level and NO concentration were measured in the rats, and the epithelial vascular cell adhesion molecule-1 （VCAM-1） expression and cell adhesiveness to the aortic endothelium were observed. Results Compared with the control group, the rats with hyperlipidemia induced by long-term high-fat diet feeding showed lower NO concentration and increased leukocyte accumulation on the endothelial surface, exhibiting also stronger and more extensive endothelial expression of VCAM-1. In contrast, the hyperlipidemic rats with fenofibrate treatment shoed significantly decreased VCAM-1 expression and leukocyte adhesion with recovery of the NO level. Conclusion NO deficiency and activation of inflammation are involved in vascular impairment in rats with high-fat diet-induced hyperlipidemia, and fenofibrate can effectively prevent atherosclerosis by restoring NO concentration and down-regulating VCAM-1 expression in these rats.