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

作　　者：张全爱 李沙[2] 王恺悌 董慧聪 卢晓飞 郭永泽[4] ZHANG Quanai;LI Sha;WANG Kaiti;DONG Huicong;LU Xiaofei;GUO Yongze(Clinical Medical College,Hebei University of Engineering,Handan 056002,China;Medical College of Hebei University of Engineering,Handan 056002,China;Xinjiang Medical University,Urumqi 830000,China;Department of Gastroenterology,Affiliated Hospital of Hebei University of Engineering,Handan 056002,China)

机构地区：[1]河北工程大学临床医学院,河北省邯郸市056002 [2]河北工程大学医学院,河北省邯郸市056038 [3]新疆医科大学,新疆维吾尔自治区乌鲁木齐市830000 [4]河北工程大学附属医院消化科,河北省邯郸市056002

出　　处：《中国全科医学》2025年第20期2538-2545,共8页Chinese General Practice

基　　金：国家自然科学基金资助项目(81800549);河北省自然科学基金资助项目(H2020402002)。

摘　　要：背景司美格鲁肽作为胰高血糖素样肽1受体激动剂之一,对于缓解非酒精性脂肪性肝病(NAFLD)的进展有很大的潜力,但是作用机制尚未明确。目的研究司美格鲁肽对肝脏脂质代谢的影响,进一步探究NAFLD的发病机制及帮助临床做出诊断和治疗。方法2022年9—11月选取30只SPF级5~8周龄雄性SD大鼠,体质量(180±20)g,大鼠适应性喂养1周后随机分为空白组、模型组和干预组,每组10只。制备NAFLD大鼠模型,干预组大鼠给予司美格鲁肽40μg/kg,溶解于0.9%氯化钠溶液皮下注射,空白组和模型组大鼠皮下注射等量0.9%氯化钠溶液。观察大鼠一般情况,苏木素-伊红(HE)染色和油红O染色观察大鼠肝组织病变情况,检测大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平,检测大鼠肝组织三酰甘油(TG)水平。反转录聚合酶链反应(RT-PCR)检测脂肪酸合成酶(FAS)、乙酰辅酶A羧化酶(ACC1)、肉毒碱棕榈酰转移酶1α(CPT1α)、乙酰辅酶A氧化酶(AOX)、脂肪酸转运蛋白36(FAT/CD36)、肝脏脂肪酸结合蛋白(LFABP)、载脂蛋白B(ApoB)、微粒体三酰甘油转移蛋白(MTTP)mRNA表达量。蛋白质印迹试验(Western blotting)检测FAT/CD36蛋白含量。结果实验期间各组动物均无死亡,空白组大鼠毛发柔顺、有光泽、精神状态良好,模型组和干预组大鼠随喂养时间增长,表现为体质量明显减轻,毛发紊乱、无光泽,活动减弱,精神萎靡。干预结束后模型组体质量低于空白组,干预组高于模型组(P<0.05)。模型组肝脏质量高于空白组,干预组低于模型组(P<0.05)。模型组ALT、AST、TG水平高于空白组,干预组ALT、AST、TG水平低于模型组(P<0.05)。模型组CPT1α、AOX、LFABP、ApoB、MTTP低于空白组,干预组FAT/CD36低于模型组(P<0.05)。模型组FAT/CD36高于空白组,干预组低于模型组(P<0.05)。结论司美格鲁肽缓解了NAFLD大鼠肝脏的脂质沉积,这可能与FAT/CD36表达下调有关。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 40μg/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,

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36 

分 类 号：R575.5[医药卫生—消化系统]