普罗布考对高脂血症兔肝功能及胆汁酸受体表达的影响

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。

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

Objective To explore the effects of probucol on liver functions and expression of farnesoid 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: Maintained highcholesterol 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 [AST,(49.68±15.84)U/L vs(81.36±22.97)U/L,P<0.01],total 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 cholest erol 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.