阿托伐他汀对高胆固醇血症兔脂肪肝形成及血清肿瘤坏死因子-α的影响

Effects of Atorvastatin on Non-alcoholic Steatohepatitis and Tumor Necrosis Factor-alpha in Serum of Hyperccholesterolemia Rabbits

目的观察阿托伐他汀对高胆固醇血症兔脂肪肝形成的影响,并探讨其可能的机制。方法 24只新西兰大白兔随机分为正常组(普通饮食12周)、高胆固醇组(高胆固醇饮食12周)及阿托伐他汀组(高胆固醇饮食8周后,在继续饲以高胆固醇饲料的基础上给予阿托伐他汀每天2.5 mg/kg,连续4周)。观察兔血脂和血清肿瘤坏死因子-α(TNF-α)水平的变化;取肝脏作病理形态学检查。结果高胆固醇组兔血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDLC)及TNF-α水平较正常组升高(P<0.01);肝脏脂肪变性程度最重(R=0.72),肝脏重量、贮脂细胞数量较正常组均增加(P<0.01);阿托伐他汀组血清TC、LDLC及TNF-α水平较高胆固醇组降低(P<0.05),肝脂变程度明显改善(R=0.53);肝脏重量、贮脂细胞数量低于高胆固醇组。结论阿托伐他汀能减轻高胆固醇血症兔肝脏脂肪变性程度,这一作用可能与其降脂同时降低血清TNF-α水平有关。

Objective To investigate the effects of atorvastatin on the formation of non-alcoholic steatohepatitis and serum TNF-α concentration of hypercholesterolemia rabbits. Methods Twenty-four New Zealand white rabbits were randomly assigned to normal group（normal diet for 12 weeks）,high cholesterol group（high-cholesterol diet for 12 weeks） and atorvastatin group（after high cholesterol diet for 8 weeks,the same cholesterol diet supplemented with atorvastatin 2.5 mg/kg/d for 4 weeks）.The serum lipid and TNF-α level of rabbits were measured.Pathomorphology in hepatic tissue were detected. Result Rabbits of high cholesterol group showed higher serum levels of total cholesterol,low density lipoprotein cholesterol and TNF-α than those of control group（P0.01）,and they also showed significantly more aggravated liver steatosis（R= 0.72）,increased liver weight s and more fat-storing cells counting than those of control group（P0.01）.Compared with high cholesterol group,atorvastatin treatment could significantly reduce the levels of serum total cholesterol,low density lipoprotein cholesterol and TNF-α（P 0.05）,and significantly improve liver steatosis（R= 0.53）,decrease liver weight s and fat-storing cells counting（P0.05）. Conclusion Our study indicated that atorvastatin therapy could reduce the degree of liver steatosis,which might be partially dependent on its lipid-lowering effect and decreasing serum TNF-α levels in hypercholesterolemia rabbits.