艾塞那肽通过调控PPARα及ACOX1表达而改善大鼠非酒精性脂肪肝病症状

基础医学与临床 ›› 2014, Vol. 34 ›› Issue (4): 464-469.

艾塞那肽通过调控PPARα及ACOX1表达而改善大鼠非酒精性脂肪肝病症状

武俊紫¹,牛世伟¹,贾亚敏²,陶文艳³,柳波³,李燕¹,李树德⁴

1. 云南省第一人民医院
2. 太原理工大学
3. 昆明医科大学
4. 昆明医科大学基础医学院

收稿日期:2013-09-02 修回日期:2013-10-24 出版日期:2014-04-05 发布日期:2014-03-31
通讯作者: 李燕 E-mail:liyanken@126.com
基金资助:
人参皂苷Rg1调控胰岛素抵抗肝脏葡萄糖输出的分子机制研究;GLP-1受体激动剂对非酒精性脂肪肝病的作用;Gln刺激肠道L细胞释放GLP-1的研究;人参皂苷Rg1治疗斯氏狸殖吸虫所致肝纤维化的机制研究

Exenatide Treatment Improves Nonalcoholic Fatty Liver Phenotype by Regulation of PPARα and ACOX1

Received:2013-09-02 Revised:2013-10-24 Online:2014-04-05 Published:2014-03-31

摘要/Abstract

摘要： 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（HFD）、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。

关键词: 艾塞那肽, 非酒精性脂肪肝病, 过氧化物酶增殖激活受体α, 酰基辅酶A氧化酶1

Abstract: Objective To observe the Exenatide effect on fat-induced nonalcoholic fatty liver disease (NAFLD) in rat. Methods 120 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, the corresponding detection kit liver function, blood lipids function, RT-PCR and western blot measured PPARα and ACOX1 expression. Results After 8 weeks of treatment, rat liver HE staining PDC, EMD and EHD have 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. Conclusion Exenatide improves NAFLD Phenotype by regulation of PPARα and ACOX1 expression.

Key words: exenatide, non-alcoholic fatty liver disease, peroxisome proliferator activated receptors α, acyl coenzyme a oxidase 1

武俊紫牛世伟贾亚敏陶文艳柳波李燕李树德. 艾塞那肽通过调控PPARα及ACOX1表达而改善大鼠非酒精性脂肪肝病症状[J]. 基础医学与临床, 2014, 34(4): 464-469.