烟酸对高脂血症兔脂肪细胞胆固醇流出和肝X受体表达的影响

Effect of niacin on HDL-induced cholesterol efflux and LXRα expression in adipocytes of hypercholesterolemic rabbits

目的探讨烟酸对高脂血症兔脂肪细胞胆固醇流出和肝 X 受体(LXR)α、过氧化物酶体增殖物激活受体(PPAR)γ mRNA 表达的影响。方法选取12只健康雄性新西兰兔给予高胆固醇饲料培养8周,建立高胆固醇兔模型后,随机分为高胆固醇组(继续饲以高胆固醇饲料6周,n=6),烟酸治疗组(在饲以高胆固醇饲料的基础上给予烟酸缓释剂0.2 g·kg^(-1)·d^(-1),共6周,n=6),另选普通饮食14周雄性新西兰兔(n=6)作为对照组。实验结束后,取皮下脂肪行脂肪细胞培养,用液体闪烁计数器检测细胞内胆固醇流出,运用逆转录聚合酶链反应检测 LXRα mRNA 的表达。此外,在体外观察不同浓度的烟酸缓释剂(0.25、0.5、1、2 mmol/L)对健康雄性新西兰兔脂肪细胞 LXRα、PPARγmRNA 的影响。结果高胆固醇组脂肪细胞胆固醇流出率(5.94±1.26)%明显低于正常对照组(12.68±1.31)%,烟酸治疗组脂肪细胞胆固醇流出升高明显(16.39±3.32)%,3组间比较差异有统计学意义。逆转录聚合酶链反应显示烟酸治疗组较高胆固醇组 LXRα mRNA 表达高,与胆固醇流出率呈正相关。体外实验亦显示,烟酸缓释剂呈浓度依赖性升高脂肪细胞 LXRα、PPARγ mRNA 的表达。结论烟酸增加高脂血症兔脂肪细胞 LXRα mRNA 的表达及细胞内胆固醇流出。

Objective To investigate the effect of niacin on HDL-induced cholesterol efflux and LXRot expression in adipocytes from hypercholesterolemic rabbits. Methods Twelve rabbits fed with highcholesterol diet for 8 weeks were randomly divided into two groups ： （ 1 ） high cholesterol group （ n = 6 ） ： maintained high cholesterol diet for 6 weeks; （2） niacin group （ n = 6 ） ： the same cholesterol diet plus niacin （0.2 g·kg^-1·d^-1） for 6 weeks. Control group （n =6） was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for adipocyte culture. RT-PCR was used to evaluate adipocytes LXRot mRNA expressions. Cholesterol efflux rate was determined through measuring release of radioactivity from H-cholesterol prelabeled cells into medium containing HDI. The direct effect of niacin on LXRot and PPARγ mRNA expression in primary rabbit adipocytes was assayed. Results High cholesterol diet resulted in decreased LXRot mRNA expressions and reduced cholesterol efflux rate in adipocytes. Six weeks of niacin treatment significantly enhanced the cholesterol efflux from adipocytes, which was related to the increased mRNA expressions of LXRot （ r = 0. 71, P 〈 0. 05 ）. In vitro study, niacin dose-dependently stimulated LXRot and PPARγ mRNA expression in cultured adipocytes and there were positive correlations between various doses of niacin-induced cholesterol efflux and LXRot and PPARγ mRNA expression （ r = 0. 83 P 〈 0. 01, r = 0. 76 P 〈 0. 05, respectively）. Conclusion LXRot and PPARγ might play an important role in cholesterol efflux from adipocytes. Niacin can up-regulate LXRot and PPARγ mRNA expressions and promote the cholesterol efflux in adipocytes from hypercholesterolemlc rabbits.