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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 effects of nicotinic acid on cholesterol efflux, hepatic X receptor (LXR) α and peroxisome proliferator - activated receptor γ (PPARγ) mRNA expression in adipocytes of hyperlipidemic rabbits. Methods Twelve healthy male New Zealand white rabbits were fed with high cholesterol diet for 8 weeks. After establishment of hypercholesterolemic rabbits, they were randomly divided into high cholesterol group (fed with high cholesterol diet for 6 weeks, n = 6), nicotinic acid treatment group Fed with high-cholesterol diet on the basis of niacin sustained-release 0.2 g · kg -1 d -1 for 6 weeks, n = 6, and another 14 weeks-old male New Zealand rabbit n = 6) as a control group. After the experiment, subcutaneous fat was cultured in adipocytes, the efflux of intracellular cholesterol was detected by liquid scintillation counter, and the expression of LXRα mRNA was detected by reverse transcription polymerase chain reaction. In addition, the effects of different concentrations of nicotinic acid sustained release (0.25,0.5,1,2 mmol / L) on LXRαand PPARγmRNA in adipocytes of healthy male New Zealand rabbits were observed in vitro. Results Cholesterol efflux rate of adipocytes from high cholesterol group (5.94 ± 1.26)% was significantly lower than that of normal control group (12.68 ± 1.31)%, while adiponectin efflux from adiponectine group was significantly increased (16.39 ± 3.32)% The difference was statistically significant. Reverse transcription polymerase chain reaction (RT-PCR) showed that the expression of LXRα mRNA in high-nicotinic acid group was higher than that in high-cholesterol group, and positively correlated with the cholesterol efflux rate. In vitro experiments also showed that nicotinic acid sustained-release agent in a concentration-dependent manner increased adipocyte LXRα, PPARγ mRNA expression. Conclusion Niacin can increase the expression of LXRα mRNA and the efflux of intracellular cholesterol in adipocytes of hyperlipemic rabbits.