齐墩果酸衍生物DKS26对非酒精性脂肪肝病模型小鼠肝组织Fndc5表达的影响  

Effect of oleanolic acid derivative DKS26 on Fndc5 expression in liver tissue of non-alcoholic fatty liver disease model mice

作　　者：韩萧萧 李晨驰 刘冉阳 唐爽 冯琳琳 韩冰 谢汝佳 杨勤 HAN Xiaoxiao;LI Chenchi;LIU Ranyang;TANG Shuang;FENG Linlin;HAN Bing;XIE Rujia;YANG Qin(Department of Pathophysiology,College of Basic Medical Sciences,Guizhou Medical University,Guiyang 550025,Guizhou,China;Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases,Guizhou Medical University,Guiyang 550025,Guizhou,China;Department of Clinical Microbiology and Immunology,School of Clinical Laboratory Science,Guizhou Medical University,Guiyang 550025,Guizhou,China)

机构地区：[1]贵州医科大学基础医学院病理生理学教研室,贵州贵阳550025 [2]贵州省常见慢性疾病发病机制及药物研究重点实验室,贵州贵阳550025 [3]贵州医科大学医学检验学院临床微生物免疫教研室,贵州贵阳550025

出　　处：《贵州医科大学学报》2023年第4期383-388,共6页Journal of Guizhou Medical University

基　　金：国家自然科学基金资助项目(81460484)。

摘　　要：目的 研究齐墩果酸衍生物DKS26对非酒精性脂肪肝病(NAFLD)模型小鼠肝组织中Ⅲ型纤连蛋白组件包含蛋白(Fndc5)表达的影响。方法 40只健康5周龄C57/BL小鼠随机均分为对照组(CON组)、模型组(MOD组)、二甲双胍对照组(MET组)和DKS26组,后3组小鼠用40%四氯化碳皮下注射加高脂饮食喂养、建立小鼠NAFLD模型,MET组和DKS26组小鼠分别给予100 mg/(kg·d)的MET和DKS26灌胃干预、CON组和MOD组小鼠给予100 mg/(kg·d)的羧甲基纤维素钠(CMC-Na)溶液灌胃干预,1次/d,共6周;末次干预后检测各组小鼠血清ALT、AST及肝组织的TG含量、脂滴沉积及肝组织学变化,Western blot法检测肝组织Fndc5蛋白表达。结果 与CON组相比,MOD组小鼠血清ALT和AST水平明显上升(P<0.01),肝组织TG含量明显上升(P<0.01),肝细胞空泡样变明显、胞质脂质沉积过多,Fndc5表达下调(P<0.05);MET和DKS26干预后,两组小鼠血清ALT、AST水平、肝组织TG含量、肝细胞空泡样变及脂质沉积较MOD组明显下降(P<0.01),且DKS26干预组小鼠血清AST水平低于MET组(P<0.05);MET组和DKS26组干预后,两组小鼠肝组织Fndc5蛋白表达较MOD组上调(P<0.05),且DKS26组比MET组更高(P<0.05)。结论 DKS26对NAFLD小鼠的肝功能指标及肝脂肪沉积有改善作用,其机制可能与调节鸢尾素(irisin)前体Fndc5表达有关。Objective To study the effect of oleanolic acid derivative DKS26 on the expression of TypeⅢdomain-containing protein 5(Fndc5)in liver tissue of non-alcoholic fatty liver disease(NAFLD)model mice.Methods Forty C57/BL mice at 5 weeks of age were randomly divided into four groups:control group(CON group),model group(MOD group),metformin control group(MET group),and DKS26 group.Mice in the latter three groups were injected subcutaneously with 40%carbon tetrachlorideand and fed a high-fat diet to establish the NAFLD model.Mice in the MET and DKS26 groups were orally administered 100 mg/(kg·d)of MET and DKS26 respectively,while mice in the CON and MOD groups were orally administered 100 mg/(kg·d)of carboxymethyl cellulose sodium(CMC-Na)solution as an intervention,once a day,for a total of 6 weeks.After the last intervention,serum ALT,AST,liver tissue TG content,lipid deposition,and liver histological changes were detected in all groups of mice.Western blot was used to detect Fndc5 protein expression in liver tissue.Results Compared to the CON group,the MOD group of mice showed significant increases in serum ALT and AST levels(P<0.01),as well as a significant increase in liver tissue TG content(P<0.01).Additionally,there were noticeable vacuolar changes in the liver cells and excess cytoplasmic lipid deposition,along with downregulation of Fndc5 expression(P<0.05).However,following interventions with MET and DKS26,both groups of mice showed significant decreases in serum ALT and AST levels,liver tissue TG content,vacuolar changes,and lipid deposition compared to the MOD group(P<0.01).Furthermore,the DKS26 intervention group showed significantly lower serum AST levels than the MET intervention group(P<0.05).Following interventions with either MET or DKS26,there was an upregulation of Fndc5 protein expression in both groups of mouse liver tissues compared to the MOD group(P<0.05),with the DKS26 group showing a higher level of upregulation than the MET group(P<0.05).Conclusion DKS26 has an improvement effect on liver f

关 键 词：非酒精性脂肪肝病 墩果酸衍生物DKS26 Ⅲ型纤连蛋白组件包含蛋白 脂质氧化 二甲双胍 

分 类 号：R735.9[医药卫生—肿瘤]