摘要
目的研究艾塞那肽对非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)大鼠的肝脏组织、胰岛素抵抗、SREBP-1、ACCα、SCD1表达的影响。方法SD大鼠予100%高脂溶液灌胃12周,造模成功后取100只随机分为NAFLD模型组(high-fat diet,HFD),艾塞那肽低剂量(exenatidelow dose,ELD)、中剂量(exenatidemiddle dose,EMD)、高剂量干预组(exenatidehigh dose,EHD)及多烯磷脂酰胆碱治疗组(positive drug polyenephosphatidylcholine,PDC),每组各20只。艾塞那肽干预组予艾塞那肽1μg、2μg、4μg/kg(大鼠体重)注射治疗,PDC予多烯磷脂酰胆碱46 mg/kg(大鼠体重)注射。4周和8周后分别处死大鼠各半,HE染色观察肝脏病理改变,测定空腹血糖、胰岛素水平,检测SREBP1、ACCα及SCD1表达。结果艾塞那肽可以改善肝脏脂肪浸润,减少脂肪颗粒,降低天门冬氨酸氨基转移酶(Aspartate aminotransferase,AST)、丙氨酸转移酶(alanine aminotransferase,ALT)(P<0.05);改善胰岛素抵抗(P<0.05);SREBP1及ACCαm RNA表达明显降低,SCD1-mRNA表达升高(P<0.05)。结论艾塞那肽可能通过调控SREBP1、ACCα、SCD1的表达,降低胰岛素抵抗,可能对NAFLD有一定的治疗作用。
Objective To study the effects of exenatide on liver tissue,insulin resistance,SREBP-1,ACCα,SCD1 expression in nonalcoholic fatty liver disease(NAFLD)rats.Methods Sprague Dawley rats were given 100%high fat solution by gavage for 12 weeks.After successful modeling,100 rats were randomly divided into model group(high-fat diet,HFD),exenatide low dose(ELD),exenatide middle dose(EMD),high-dose intervention(EHD)and polyene phosphatidylcholine(PDC),with 20 rats in each group.Three groups of ELD,EMD,EHD were injected under the skin with different exenatide doses:1μg,2μg and 4 ug/kg rat body weight.The group of PDC was injected with PDC 46 mg/kg rat body,and the group of HFD was given saline solution.rats were sacrificed after 4 and 8 weeks.The liver tissue was stained with HE,the fasting blood glucose and insulin levels were measured,and the expressions of SREBP1,ACCαand SCD1 were detected.Results Exenatide can improve liver fat infiltration,reduce fat granules,decrease aspartate aminotransferase(AST),alanine aminotransferase(ALT)(P<0.05),reduce insulin resistance(P<0.05),decrease SREBP1 and ACCαmRNA expression,and increase SCD1 mRNA expression(P<0.05).Conclusion Exenatide can attenuate the insulin resistance by regulation of SREBP1,ACCαand SCD1 expression,and may have some therapeutic effect on NAFLD.
作者
梁蔚蔚
李晓波
李燕
刘华
武俊紫
LIANG Wei-wei;LI Xiao-bo;LI Yan;LIU Hua;WU Jun-zi(Dept.of Geriatric Medicine,The First People’s Hospital of Yunnan Province,Kunming Yunnan 650032,China)
出处
《昆明医科大学学报》
CAS
2020年第7期23-29,共7页
Journal of Kunming Medical University
基金
云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目(2011FB225,2013FZ183)。
