普罗布考对高脂血症兔肝功能及胆汁酸受体表达的影响  

Effects of probucol on liver function and expression of farnesoid X receptor in hypercholesterolemic rabbits

作　　者：洪绍彩[1] 赵水平[1] 刘琼[1] 

机构地区：[1]中南大学湘雅二医院心内科,湖南长沙410011

出　　处：《中国心血管杂志》2006年第4期241-244,共4页Chinese Journal of Cardiovascular Medicine

摘　　要：目的观察普罗布考对高脂血症兔肝功能及肝脏胆汁酸受体(FXR)mRNA表达的影响。方法16只新西兰大白兔给予高脂饲料饲养8周后,随机分为:(1)高胆固醇组(n=8):继续饲以高脂饲料6周;(2)普罗布考组(n=8):在饲以高脂饲料的基础上给予1%普罗布考,共6周。正常饲料组(n=8):另选8只饲以普通饲料14周的兔为对照组。动态观察肝功能变化,实验结束后,采用半定量逆转录聚合酶链式反应(RT-PCR)法测定肝脏FXR mRNA的表达。结果①普罗布考治疗6周后,血清总胆固醇,低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)均明显下降;②普罗布考组谷丙转氨酶(ALT)(45.34±14.91)U/L及谷草转氨酶(AST)(49.68±15.84)U/L,较高胆固醇组[ALT(67.20±17.34)U/L,AST(81.36±22.97)U/L]均明显降低,P均<0.01;③与高胆固醇组比较,普罗布考组血清总胆汁酸(TBA)(46.11±18.58)mmol/L vs(56.34±20.67)mmol/L,总胆红素(T-BIL)均明显降低,为(3.04±1.06)mmol/L vs(5.34±1.38)mmol/L,P均<0.05;④肝脏FXR mRNA的表达明显增加,为0.86±0.05 vs 0.62±0.06,P=0.018。结论普罗布考具有护肝作用,其降低HDL-C可能与上调FXRmRNA的表达有关。Objective To explore the effects of probucol on liver functions and expression of famesoid X receptor （FXR） in livers of hypercholesterolemic rabbits. Methods 16 male New Zealand white rabbits were fed with 1% cholesterol, 7.5 % protein, 8% lard diet for 8 weeks. Then they were randomly divided into two groups： （ 1 ） High cholesterol group： Mainrained high-cholesterol diet for 6 weeks; （2） Probucol group： The same cholesterol diet supplemented with 1% probucol for 6 weeks. Control group was fed with normal diet for 14 weeks. FXR mRNA expression were evaluated by RT-PCR. Results Compared with control group, rabbits fed with high-cholesterol diet showed higher levels of serum total cholesterol （TC）, low-density lipoprotein cholesterol （LDL-C） and HDL-C, all of which were significantly reduced by probucol. Compared with high cholesterol group, the levels of alanine transaminase [ALT, （45.34 ± 14.91 ）U/L vs （67.20 ± 17.34）U/L, P〈0.01], aspartate transaminase lAST,（49.68± 15.84）U/Lvs （81.36±22.97）U/L, P〈0.01], to- tal bile acid [TBA, （46.11 ± 18.58） mmol/L vs （56.34 ± 20.67） mmol/L, P = 0. 042] and total bilirubin [T-BIL, （3.04 ± 1.06）mmol/L vs （5.34 ± 1.38）mmol/L, P = 0. 021 ] were significantly dropped after six weeks treatment with probucol. The mRNA expressions of FXR in liver were up-regulated in probucol group as compared with high cholesterol group （0.86 ± 0.05 vs 0.62 ± 0.06, P = 0.018）. Conclusions Probucol can improve liver function, and the reduction of HDL-C may be due to up-regulated FXR mRNA expression in liver.

关 键 词：普罗布考 胆汁酸 胆固醇 胆汁酸受体 肝功能 

分 类 号：R96[医药卫生—药理学]