烟酸对高脂血症兔瘦素、过氧化体增殖物激活型受体γ和CD36表达的影响

Effect of Niacin on Adipocyte Leptin,Peroxisome Proliferator-Activated Receptor γ and CD36 in Hypercholesterolemic Rabbits

目的探讨烟酸对高脂血症兔血清瘦素及皮下脂肪组织瘦素、过氧化体增殖物激活型受体γ及CD36 mRNA表达的影响。方法12只健康雄性新西兰兔给予高胆固醇饮食饲养8周后,随机分为高脂组和烟酸组:高脂组继续饲以高胆固醇饲料6周;烟酸组在饲以高胆固醇饲料的基础上给予烟酸0.2g/(kg.d),共6周。另选择普通饮食14周兔(n=6)作为对照组。实验结束后,取腹股沟处皮下脂肪组织称重并冻存,用酶联免疫吸附法测定血清及脂肪细胞培养基瘦素水平;半定量逆转录聚合酶链反应测定脂肪组织瘦素、过氧化体增殖物激活型受体γ及CD36mRNA的表达。此外,在体外观察不同浓度的烟酸对高脂兔脂肪细胞瘦素、过氧化体增殖物激活型受体γ及CD36 mRNA的表达。结果高脂组兔血清及脂肪组织瘦素水平明显高于正常对照组,烟酸治疗6周后可降低血清及脂肪组织瘦素水平。逆转录聚合酶链反应表明烟酸组较高脂组瘦素mRNA表达降低,瘦素mRNA与过氧化体增殖物激活型受体γmRNA和CD36 mRNA的表达呈负相关。体外实验亦表明,烟酸呈剂量依赖性地降低脂肪细胞瘦素mRNA表达,并剂量依赖性地上调过氧化体增殖物激活型受体γ及CD36 mRNA的表达。结论烟酸治疗能降低高脂血症兔血清及脂肪分泌瘦素水平,上调过氧化体增殖物激活型受体γ及CD36 mRNA的表达。

Aim To investigate the effect of niacin on serum leptin levels in hypercholesterolemic rabbits and the expression of leptin, peroxisome proliferator-activated receptor γ （PPART） and CD36 in adipocytes from hypereholesterolemic rabbits. Methods Twelve rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into two groups： high cholesterol group （ n = 6） maintained on high cholesterol diet for 6 weeks, niacin group （ n = 6） fed with the same cholesterol diet plus niacin[0.2g/（kg·d）]for 6 weeks. Controlgroup（n=6） was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for RNA analysis. Leptin levels in serum and adipocytes culture supernatant were measured by enzyme linked immunesorbent assay （ELISA）. Reverse transcription polymerase chain reaction （RT-PCR） was used to evaluate leptin, PPARγ and CD36 mRNA expressions in adipose and adipocytes. Results Compared with control group, rabbits fed with high cholesterol diets showed higher levels of serum and adipocyte leptin, all of which were significantly reduced by niacin treatment. Leptin mRNA expression of adipose was significantly lower in rabbits treated with niacin than those fed with high cholesterol diet. Leptin mRNA expression of hypereholesterolemic rabbits by niacin was negatively correlated with the mRNA expression of PPARγ and CD36 by niacin. Niacin dose-dependently inhibited leptin secretion and increased CD36 and PPARγ expression in cultured adipocytes. Conclusion Niacin can reduce serum level and adipose mRNA expression of leptin, and upregulate PPARγ and CD36 mRNA expression in hypercholesterolemic rabbits.