辛伐他汀对高脂血症兔肝脏病理形态学及PPARγ表达的影响

The Effect of Simvastatin on Pathomorphology and PPARγ Expression in Hepatic Tissue of Hyperlipidemic Rabbits

【目的】观察辛伐他汀对高脂血症兔肝脏病理形态学及PPARγ表达的影响。【方法】40只日本大耳白兔随机分为正常组、模型组及辛伐他汀组,高脂饲养建立兔高脂血症动物模型。实验结束时测定血脂浓度,取肝脏作病理形态学检查,用RT-PCR和蛋白质免疫印迹(Western blot)方法观察肝脏PPARγ基因和蛋白表达的变化。【结果】模型组兔血清总胆固醇(TC)、甘油三脂(TG)及低密度脂蛋白胆固醇(LDL-C)水平较正常组升高(P<0.01),肝脏脂肪变性程度最重(R=0.68),肝脏重量、贮脂细胞数量较正常组均增加(P<0.01);辛伐他汀组血清TC、TG及LDL-C水平较模型组降低(P<0.01),肝脂变程度明显改善(R=0.48),肝脏重量(P<0.05)、贮脂细胞数量(P<0.01)低于模型组。模型组兔肝脏PPARγ基因和蛋白表达水平较正常组增加(P<0.05),辛伐他汀组PPARγ基因和蛋白表达水平高于模型组(均P<0.05)。【结论】辛伐他汀能减轻高脂血症兔肝脏脂肪变性程度,这一作用可能与其降脂同时上调肝脏PPARγ表达有关。

[Objective]To explore the effect of simvastatin on pathomorphology and peroxisome proliferator-activated receptor γ（PPARγ）expression in hepatic tissue of hyperlipidemic rabbits. [Methods]Forty Japanese white rabbits were randomly assigned to normal group, hyperlipidemic group and simvastatin group. The hyperlipidemic models of rabbits were set up by feeding with high fat diet. The serum lipid levels and pathomorphology in hepatic tissue were detected. The changes of mRNA and protein expression of PPARγ in hepatic tissue were assayed by RT-PCR and Western blot respectively. [Results] Hyperlipidemic rabbits showed higher serum levels of total cholesterol, triglyceride and low density lipoprotein cholesterol than those of control group （ P 〈0.01）. and they also showed significantly more aggravated liver steatosis （R=0. 68）, increased liver weights and more fat-storing cells counting than those of control group （P〈0.01）. Compared with hyperlipidemie rabbits, simvastatin treatment could significantly reduce the levels of serum total cholesterol, triglyceride and low density lipoprotein cholesterol （ P〈0.01 ）. and significantly improved liver steatosis （R=0.48）, decreased liver weights and fat-storing cells counting. The expressions of PPARγmRNA and protein in hepatic tissue were up-regulated in hypcrlipidemic group compared with those of control group （ P〈0.05）. Meanwhile the expressions of PPARγmRNAand protein in hepatic tissue were higher in simvastatin group than in hyperlipidemic group （ P 〈0.05）. [Conclusion]Simvastatin therapy could reduce the degree of liver steatosis,that might be partially dependent on its lipid-lowering effect and up-regulating the expression of PPARγ in hepatic tissue.