中国全科医学2025，Vol.28Issue(20)：2538-2545,8.DOI:10.12114/j.issn.1007-9572.2023.0534
司美格鲁肽在蛋氨酸胆碱缺乏饮食诱导的非酒精性脂肪性肝病大鼠肝脏脂质代谢中的研究
Effect of Semaglutide in Hepatic Lipid Metabolism of Rats in a Methionine-choline Deficient Diet-induced Non-alcoholic Fatty Liver Disease Model
摘要
Abstract
Background Semaglutide,as one of the glucagon-like peptide-1(GLP-1)receptor agonists,has significant potential for alleviating the progression of non-alcoholic fatty liver disease(NAFLD).However,its mechanism of action remains unclear.Objective To investigate the effect of semaglutide on hepatic lipid metabolism,further explore the pathogenesis of NAFLD and help clinical diagnosis and treatment.Methods Between September and November 2022,30 SPF-grade male SD rats,aged 5-8 weeks with a body weight of(180±20)g,were acclimatized for one week and then randomly divided into three groups of control,model,and intervention,with 10 rats in each.The NAFLD rat model was prepared,and the intervention group received semaglutide at 40 μg/kg dissolved in 0.9%saline solution subcutaneously.The control and model groups received an equivalent volume of 0.9%saline subcutaneously.The general condition of the rats was observed,with hematoxylin-eosin(HE)staining and Oil Red O staining to examine liver tissue lesions.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and liver tissue triglyceride(TG)levels were measured.Real-time polymerase chain reaction(RT-PCR)was used to detect mRNA expression of fatty acid synthase(FAS),acetyl-CoA carboxylase 1(ACC1),carnitine palmitoyltransferase 1α(CPT1α),acyl-CoA oxidase(AOX),fatty acid transport protein 36(FAT/CD36),liver fatty acid-binding protein(LFABP),apolipoprotein B(ApoB),and microsomal triglyceride transfer protein(MTTP).Western blotting assay was used to detect FAT/CD36 protein levels.Results There was no death of animals in all groups during the experimental period,and the rats in the control group exhibited smooth and glossy fur with good spirit,while the rats in the model group and intervention group showed a significant reduction in body weight,disorganized and lusterless hair,reduced activity and depressed spirit with the increase in feeding time.The body weight of the model group was lower than that of the control group at the end of the intervention,and the intervention group was higher than that of the model group(P<0.05).The liver weight of the model group was higher than the control group,and lower in the intervention group(P<0.05).The levels of ALT,AST,and TG were higher than those in the model group than in the control group,and lower in the intervention group(P<0.05).The levels of CPT1α,AOX,LFABP,ApoB,and MTTP were lower in the model group than in the control group,and the level of FAT/CD36 was lower in the intervention group(P<0.05).The model group had higher levels of FAT/CD36 than the control group,and the intervention group had lower levels than the model group(P<0.05).Conclusion Semaglutide alleviated hepatic lipid deposition in NAFLD rats,potentially related to the downregulation of FAT/CD36 expression.关键词
非酒精性脂肪性肝病/司美格鲁肽/脂质代谢/脂肪酸转运蛋白36Key words
Nonalcoholic fatty liver disease/Semaglutide/Lipid metabolism/Fatty acid translocase36分类
医药卫生引用本文复制引用
张全爱,李沙,王恺悌,董慧聪,卢晓飞,郭永泽..司美格鲁肽在蛋氨酸胆碱缺乏饮食诱导的非酒精性脂肪性肝病大鼠肝脏脂质代谢中的研究[J].中国全科医学,2025,28(20):2538-2545,8.基金项目
国家自然科学基金资助项目(81800549) （81800549）
河北省自然科学基金资助项目(H2020402002) （H2020402002）
