非诺贝特对兔脂肪细胞摄取及降解氧化型低密度脂蛋白及CD36表达的影响

The Effects of Fenofibrate on Endocytic Uptake and Degrade of Oxidized Low Density Lipoprotein in Adipocytes and the Expression of CD36

为了解非诺贝特对高胆固醇血症兔脂肪细胞摄取及降解氧化型低密度脂蛋白的影响并探讨其可能机制 ,将 10只新西兰大白兔给予高胆固醇饲料饲养 8周后 ,随机分为高胆固醇组和非诺贝特治疗组 ,非诺贝特组在饲以高胆固醇饲料的基础上给予非诺贝特 (每天 30mg kg) ,共 4周。另设普通饮食对照组 5只。实验结束后 ,取皮下脂肪组织行脂肪细胞培养 ,放射配基法测定脂肪细胞对氧化型低密度脂蛋白的摄取及降解 ,半定量逆转录—聚合酶链反应测定脂肪细胞CD36及过氧化体增殖物激活型受体γmRNA的表达。结果发现 ,3组兔脂肪细胞摄取及降解1 2 5Ⅰ 氧化型低密度脂蛋白均呈现一浓度依赖性饱和型曲线 ,高胆固醇组脂肪细胞摄取及降解1 2 5Ⅰ 氧化型低密度脂蛋白明显低于对照组 ;非诺贝特组脂肪细胞摄取及降解1 2 5Ⅰ 氧化型低密度脂蛋白高于高胆固醇组 ,但仍低于对照组 ,3组间比较差异有显著性 (P <0 .0 5 )。逆转录聚合酶链反应发现 ,高胆固醇组过氧化体增殖物激活型受体γ及CD36mRNA表达降低 ,非诺贝特组CD36mRNA表达与对照组相似。以上提示 ,非诺贝特能改善高胆固醇血症兔脂肪细胞摄取及降解1 2 5Ⅰ 氧化型低密度脂蛋白 ,并上调CD36mRNA的表达。

Aim To explore the effect of fenofibrate on oxidized low density lipoprotein (ox-LDL) uptake in adipocytes from hypercholesterolemia rabbits and the expression of CD36. Methods 10 male New Zealand white rabbits were fed with 1% cholesterol, 7.5% protein, 8% lard diet for 8 weeks, and were randomly divided into two groups: ① high cholesterol group: maintained cholesterol diet for 4 weeks; ② treatment group: the same cholesterol diet supplemented with fenofibrate (30 mg/kg/day) for 4 weeks. And control group was fed with normal diet for 12 weeks. Subcutaneous adipose tissues were collected for adipocytes culture. CD36 and PPARγ mRNA expression were evaluated by RT-PCR. Results The specific cell association and degradation of 125 Ⅰ ox-LDL in adipocytes from the three groups exhibited a dose-dependent saturation pattern. The endocytic uptake and degradation of 125 Ⅰ ox-LDL in adipocytes from high-cholesterol groups were inhibited; fenofibrate treatment enhanced the 125 Ⅰ ox-LDL uptake and degradation in adipocytes from hypercholesterolemia rabbits. There were obviously difference among the three groups (P<0.05). The expression of PPARγ and CD36 mRNA in adipocytes were down-regulated in high cholesterol group and the CD36 mRNA expression in adipocytes of treatment group was similar to the control group. Conclusion Fenofibrate treatment improved the ox-LDL uptake and degradation in adipocytes from hypercholesterolemia rabbits and up-regulated CD36 mRNA expression in adipocytes.