卡托普利对非酒精性脂肪性肝病大鼠肝细胞脂肪变性的影响

目的 研究卡托普利对非酒精性脂肪性肝病(NAFLD)大鼠肝细胞脂肪变性的影响。方法 随机将64只大鼠分为对照组16只(普通饲料喂养和生理盐水灌胃)、模型组16只(高脂饲料和生理盐水灌胃)、卡托普利处理组16只和罗格列酮处理组16只。给药6 w后取血清和肝组织,检测肝组织细胞色素氧化酶P4502E1(CYP2E1)mRNA水平及血清丙二醛(MDA)和谷胱甘肽(GSH)水平。结果 模型组肝细胞体积增大,见广泛性脂肪变性和细胞水肿,而卡托普利处理组大部分肝细胞排列正常,可见少量的脂肪变性,部分细胞水肿;卡托普利处理组血清AST、ALT、TC和TG水平分别为(94.1±15.6)U/L、(27.3±6.2)U/L、(1.4±0.2)mmol/L和(1.0±0.2)mmol/L,显著低于模型组【分别为(134.4±35.1)U/L、(35.2±7.1)U/L、(1.8±0.4)mmol/L和(1.4±0.2)mmol/L,P＜0.05】;卡托普利处理组肝湿重、肝指数和肝组织CYP2E1 mRNA水平分别为(11.7±2.1)g、(2.3±0.3)%和(1.8±0.2),显著低于模型组【分别为(14.3±2.0)g、(2.6±0.2)%和(2.3±0.1),P＜0.05】;卡托普利处理组血清MDA水平为(7.6±2.5)nmol/L,显著低于模型组【(12.1±2.6)nmol/L,P＜0.05】,而血清GSH水平为(41.0±17.5)mg/L,显著高于模型组【(22.2±10.2)mg/L,P＜0.05】。结论 卡托普利可有效减轻非酒精性脂肪性肝病大鼠肝细胞脂肪变性程度,可能与纠正脂代谢紊乱、恢复肝功能、增强抗氧化应激能力有关。

Effect of captopril on steatosis of hepatocytes in rats with nonalcoholic fatty liver diseases

Objective The aim of this study was to investigate the effects of captopril on hepatocellular steatosis in rats with nonalcoholic fatty liver disease(NAFLD).Methods 64 male Sprague-Dawley rats were randomly divided into four groups with 16 in each,and the rats in control were fed with normal diet or with high-fat diet for NAFLD model,in which were intragastricly administered with normal salt(model),captopril or rosiglitazone for six weeks.The hepatic cytochrome oxidase P4502E1(CYP2E1)mRNA was detected,and serum malondialdehyde(MDA)and glutathione(GSH)levelswere assayed.Results The extensive steatosis and cell edema were found in themodel group,while in the captopril-intervened group,the hepatocytes were arranged normally,with a small amount of steatosis and decreased cells edema;serum aspertate aminotransferase(AST),alanine aminotransferase(ALT),total cholesterol(TC)and total glycerin(TG)levels in the captopril-intervened group were(94.1±15.6)U/L,(27.3±6.2)U/L,(1.4±0.2)mmol/L and(1.0±0.2)mmol/L,significantly lower than【(134.4±35.1)U/L,(35.2±7.1)U/L,(1.8±0.4)mmol/Land(1.4±0.2)mmol/L,respectively,P<0.05】in the model;the liver wet weight,liver index and hepatic CYP2E1 mRNA levels in captopril-intervened group were(11.7±2.1)g,(2.3±0.3)%and(1.8±0.2),significantly lower than【(14.3±2.0)g,(2.6±0.2)%and(2.3±0.1),respectively,P<0.05】in the model;serum MDA level was(7.6±2.5)nmol/L,significantly lower than【(12.1±2.6)nmol/L,P<0.05】,while serum GSH level was(41.0±17.5)mg/L,significantly higher than【(22.2±10.2)mg/L,P<0.05】in the model.Conclusion Captopril could effectively reduce the steatosis of hepatocytes in rats with nonalcoholic fatty liver disease,which might be related to the modulation of lipid metabolism disorder,the restoration of liver function and the enhancement of anti-oxidative stress.