非诺贝特在非酒精性脂肪性肝病大鼠中的作用探讨

目的高脂饮食构建NAFLD大鼠模型,观察非诺贝特对NFALD大鼠血清学肝功、血脂及肝脏病理的影响。方法将27只雄性SD大鼠随机分为正常组(N组)、病理组(B组)及非诺贝特组(F组),每组9只,分别予正常饮食及高脂饮食建立NAFLD模型。于4、8、12周后,每组各处死大鼠3只,称体重、肝湿重,计算肝指数;8周后测定血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、三酰甘油(TG)、总胆固醇(TC);肝脏病理切片行HE染色,观察病理改变。F组第5周开始药物干预。结果 8周时B组大鼠体重及肝指数高于N组,差异有统计学意义(P<0.05),F组肝指数低于B组,差异有统计学意义(P<0.05);12周时N组与F组大鼠肝指数组间比较差异无统计学意义(P>0.05),B组大鼠体重和肝指数大于N组,差异有统计学意义(P<0.05)。血清学指标:8周时N组与F组AST、ALT、TG、TC比较差异无统计学意义(P>0.05),B组AST、ALT、TG、TC明显高于N组,且差异有统计学意义(P<0.05)。12周时B组AST、ALT、TG、TC明显高于N组,差异有统计学意义(P<0.05),B组ALT、TG高于F组,差异有统计学意义(P<0.05),F组与N组AST、ALT、TC、TG差异无统计学意义(P>0.05)。结论改良法高脂饮食诱导SD大鼠非酒精性脂肪性肝病,造模成功;非诺贝特对NAFLD大鼠的肝脏酶学、血脂及病理学均有一定改善。

Mechanism of fenofibrate in rat model of non-alcoholic fatty liver disease

Objective To establish a rat model for non-alcoholic fatty liver disease (NAFLD) and evaluate the effectiveness of fenofibrate treatment on NAFLD,based on liver enzyme tests,blood lipid levels and liver pathology of the NAFLD rats after treatment with fenofibrate. Methods A total of 27 male SD rats were randomly divided into 3 groups,with 9 rats in each group,which were respectively assigned as normal group (group N),pathological group ( group B) and fenofibrate group ( group F) . Group N was given a normal diet,while both group B and group F were fed with a high fat diet to create the NAFLD model. Three rats from each group were sacrificed after 4 weeks,8 weeks and 12 weeks,respectively. The body mass,liver weight and liver index were recorded. The serum levels of aspartate aminotransferase ( AST) ,alanine aminotransferase ( ALT) ,triglycerides ( TG) and total cholesterol ( TC) were deter-mined after 8 weeks. HE staining was done on liver tissue samples to observe for pathological changes. Group F was treated with fenofibrate on the fifth week. Results After 8 weeks, a significantly higher body mass and liver index were observed in rats of group B compared to group N (P<0. 05). The average liver index of rats in group F was low-er than group B (P<0. 05). At the 12th week,the liver indexes of rats from both group N and group F were similar with no significant difference ( P>0. 05 ) , while group B had a significantly higher liver index and body mass index compared to group N (P <0. 05). Serological indicators:measurements of AST,ALT,TG and TC taken at the 8th week were comparable between group F and group N (P>0. 05). After 8 and 12 weeks,group B showed remarkably higher levels of AST,ALT,TG and TC compared to group N (P<0. 05). At the 12th week,the levels of ALT and TG in group F were significantly lower than group B (P<0. 05). At the same time,there was no statistical difference in levels of AST,ALT,TG and TC between group F and group N (P>0. 05). Conclusion An improved rat model of NAFLD is successfully established by administration of high-fat diet to SD rats. Serological indicators,including levels of ALT,AST,TG and TC,as well as pathological findings,show that fenofibrate is an effective treatment for NAFLD.