艾塞那肽通过调控PPARα及ACOX1改善大鼠非酒精性脂肪肝病症状

Exenatide treatment improves nonalcoholic fatty liver phenotype by regulation of PPARα and ACOX1

目的研究艾塞那肽对高脂诱导的大鼠非酒精性脂肪肝病(NAFLD)的作用。方法120只SD大鼠随机分为对照组(CON)、模型组(1FD)、艾塞那肽低、中、高剂量干预组(ELD、EMD、EHD)和阳性药物多烯磷脂酰胆碱治疗组(PDC),每组20只,成功复制NAFLD模型后,给予相应治疗,治疗4周和8周后分别处死大鼠各半,肝脏切片HE染色、相应试剂盒检测肝功能、血脂指标,RT-PCR及Western blot测定PPARα及ACOX1的mRNA和蛋白表达。结果治疗8周后,肝脏HE染色除ELD外,PDC、EMD及EHD看不到任何脂肪颗粒浸润;治疗4周后,PDC、ELD、EMD以及EHD组与HFD组相比,肝功能指标AST、ALT与CHE,血脂指标CHOL与TG,明显降低(P<0.05),8周后进一步降低;治疗后肝脏组织过氧化物酶增殖激活受体α(PPARα)和酰基辅酶A氧化酶1(ACOX1)表达有显著改善。结论艾塞那肽可通过调控PPARα及ACOX1表达改善NAFLD大鼠症状。

Objective To observe the exenatide effect on fat-induced nonalcoholic fatty liver disease （NAFLD） in rat. Methods One hundred and twenty SD rats were randomly divided into control group （CON）, model group （ HFD）, exenatide low, medium, high dose group （ ELD, EMD, EHD） and polyene phosphatidylcholine treatment group （ PDC）, each group was 20. After successfully established NAFLD, given appropriate treatment, half of the rats were sacrificed after 4 and 8 weeks. HE staining of liver slices, liver function test, blood lipids function, RT-PCR Western blot for PPARcx and ACOX1 expression were performed. Results After 8 weeks of treatment, rat liver HE staining PDC, EMD and EHD had not any fat particles infiltration ; after 4 weeks treatment, liver function AST, ALT and CHE, serum lipids CHOL and TG compared with HFD group, PDC, ELD, EMD and EHD, P 〈 0.05,8 weeks further reduced ; liver peroxisome proliferator-activated receptor α （PPARα） and acyl coenzyme A oxidase 1 （ACOX1） expression has also undergone a significant improvement. Conclusions Exenatide improves NAFLD Phenotype by regulation of PPARα and ACOX1 expression.