瑞舒伐他汀对兔高脂血症胆固醇流出的影响及其机制  

Effect of Rosuvastatin on Cholesterol Efflux in Rabbits with Hypercholesterolemia and Its mechanism

作　　者：阳军[1] 邓志雄[1] 范文娟[1] 刘征宇[1] 

机构地区：[1]湖南省人民医院心内科,湖南长沙410005

出　　处：《医学临床研究》2013年第1期7-10,共4页Journal of Clinical Research

基　　金：湖南省科技厅科技项目（2009SK3078）资助

摘　　要：【目的】探讨瑞舒伐他汀对高脂血症免脂肪细胞胆固醇流出的影响及其机制。【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，随机分为两组。①高胆固醇组（A组）：继续饲以高胆固醇饲料6周；②瑞舒伐他汀治疗组（B组）：在饲以高胆固醇饲料的基础上给予瑞舒伐他汀4mg／（kg·d），共6周；另选普通饮食14周雄性新西兰兔（n=4）作为对照组（c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率（CER），应用反转录多聚酶链反应（RT-PCR）检测过氧化物酶体增殖物激活受体y（PPARy）、肝X受体a（LXRd）LXRαmRNA的表达。此外，在体外观察不同浓度的瑞舒伐他汀（0．01、0．1、1、10μmol／L）对健康雄性新西兰兔脂肪细胞PPARy、LXRdmRNA表达的影响。【结果】A组脂肪细胞CER（5．73±1．06）％明显低于对照组（10．16±1．35）％，B组脂肪细胞CER升高明显（14．59±3．27）％，三组间比较差别有显著性（P〈0．05）。RT—PCR显示B组较A组PPARymRNA表达升高，与CER呈正相关。体外实验亦显示，瑞舒伐他汀呈浓度依赖性升高脂肪细胞LxRa、PPARymRNA的表达。【结论】瑞舒伐他汀增加高脂血症兔脂肪细胞PPAR7和LXRccmRNA的表达及细胞内胆固醇流出。[Objective]To explore the effect of rosuvastatin on cholesterol efflux in adipocytes of rabbits with hypercholesterolernia. [Methods] A total of 12 male New Zealand rabbits fed with high-cholesterol diet for 8 weeks for the establishment of rabbit model with hypercholesterolemia were randomly divided into two groups. High cholesterol group（group A） maintained high cholesterol diet for 6 weeks. Rosuvastatin group （Group B） was given cholesterol diet plus rosuvastatin 4rng/kg. d for 6 weeks. Male New Zealand rabbits fed with normal diet for 14 weeks were chosen as control group（group C, n =4）. After the experiment, subcuta- neous adipose was collected for adipocyte culture. Cholesterol efflux rate（CER） was determined by using liquid luminescent counter. RT-PCR was used to determine the expression of peroxisome proliferator-activated recep- tor-7（PPART） and liver X receptor-a（LXRa） mRNA. In addition, the effect of different concentration of rosu- vastatin（0.01, 0.1, 1 and 10 tlmol/L, respectively） on the expression of PPAR7 and LXRa mRNA in adipo- cytes of health male New Zealand rabbits was observed in vitro. [Results] CER in adipocytes of group A（5.73 ± 1.06 %） was obviously lower than that in control group（10.16 ±1.35%）, while CER in adipocytes of group B increased more obviously（14.59 ± 3.27 %）, and there were significant differences among three groups（ P〈0.05）. RT-PCR showed that the expression of PPARγ mRNA in group B was higher than that in group A, and had positive correlation with CER. In vitro experiment also showed that rosuvastatin increased the expres- sion of LXRα and PPARγ mRNA in dose-dependent manner. [Conclusion] Rosuvastatin can increase the ex- pression of PPARγ and LXRα mRNA and cholesterol efflux in adipocytes of rabbits with hypercholesterolemia.

关 键 词：高脂血症 胆固醇 兔 

分 类 号：R589.21[医药卫生—内分泌]