氧化低密度脂蛋白对血管平滑肌细胞生物学功能改变的影响及阿托伐他汀干预作用

The effect of oxidized low density lipoprotein on rabbit vascular smooth muscle cell biological function and the pharmacological mechanism of atorvastatin

目的 :探讨氧化低密度脂蛋白 (oxLDL)对血管平滑肌细胞 (VSMC)分泌细胞因子的影响及三羟基三甲基戊二酰辅酶A抑制剂阿托伐他汀 (atorvastatin)的作用机制。方法 :兔血管平滑肌细胞分 6组处理。以酶联免疫法检测培养上清液中细胞因子TNFα、IL 6、IL 8水平。结果 :oxLDL(5 0 μg/ml)对TNFα、IL 6、IL 8分泌水平的增加于刺激后 1h即增至 1 2～ 1 4倍 (分别P >0 0 5 ,P <0 0 1,P <0 0 1) ,8h达 6 4～ 8 5倍 ,2 4h仍高达 1 2 6～ 5 0 5倍 (均P <0 0 1)。阿托伐他汀可完全逆转oxLDL的上述促细胞因子分泌作用。阿托伐他汀在浓度为 0 0 5～ 1μmol/L范围内 ,使各因子水平降低 (与对照组比较均P <0 0 5 ) ,此作用可被MVA阻止。 结论 :oxLDL可促进兔VSMC分泌细胞因子TNFα、IL 6和IL 8,他汀类药物阿托伐他汀可能通过抑制基础及oxLDL刺激的细胞因子分泌对VSMC生物学功能发挥较全面调控效用。

Objective:To investigate the effect of oxidized low density lipoprotein(oxLDL) on cytokins secretion of vascular smooth muscle cell (VSMC) and the intervention action of HMG-CoA reductase inhibitor,atorvastatin. Methods:Rabbit aortic VSMC was cultured in 6 groups. The level of tumor necrosis factore alpha(TNFα),interleukin-6(IL-6) and interleukin-8(IL-8) were evaluated using ELISA method. Results:oxLDL increased the secretion of TNFα,IL-6 and IL-8 by 1.2～1.4-fold within 1 hour, reached to peak of 6.4～8.5-fold and sustained as high as 1.26～5.05-fold at 24 hours. In a concentration range of 0.05～1μmol/L,atorvastatin decreased the cytockins secretion in a concentration dependent manner, which could be abolished by cholesterol precurssor mevalonate(MVA). Atorvastatin can reverse the above effects of oxLDL.Conclusions:oxLDL increase secretion of TNFα,IL-6 and IL-8. Atorvastatin can inhibit cytokins secretion stimulated with or without oxLDL by impeding the synthesis of MVA.