丁香酚对2型糖尿病小鼠的降血糖作用及肝脏糖脂代谢信号转导通路调控  

The hypoglycemic effect of eugenol on type 2 diabetic mice and regulation of signaling transduction pathway of glucose and lipid metabolism in liver

作　　者：张金山 金国范 刘艳 张立会 权海燕[1] ZHANG Jin-shan;JIN Guo-fan;LIU Yan;ZHANG Li-hui;QUAN Hai-yan(Central Laboratory of Affiliated Hospital of Yanbian University,Yanji,Jilin 133000,China;Pharmacy Dept,Yilan Town Central Health Center,Yanji,Jilin 133000,China)

机构地区：[1]延边大学附属医院中心实验室,吉林延吉133000 [2]延吉市依兰镇中心卫生院药局,吉林延吉133000

出　　处：《中国药理学通报》2022年第12期1875-1881,共7页Chinese Pharmacological Bulletin

基　　金：吉林省自然科学基金资助(No 20220101336Jc);国家自然科学基金资助项目(No 81560605);吉林省科技厅科技发展计划项目青年科研基金项目(No 20150520148JH)。

摘　　要：目的研究丁香酚对2型糖尿病(type 2 diabetes mellitus,T2DM)小鼠的降血糖作用及肝脏糖脂代谢的影响,并探讨可能的作用机制。方法采用长期高脂饲料诱导的T2DM模型,将其分为4组,每周测各组小鼠血糖与体质量1次。6周后,解剖各组小鼠肝组织并称量小鼠肝质量及体质量;检测肝指数、肝脏中脂代谢及肝功能指标;进行口服葡萄糖耐量试验;检测血清中血糖、胰岛素、甘油三酯、胆固醇、抵抗素、瘦素、胃饥饿素、胰高血糖素以及纤溶酶原激活物抑制剂-1水平;HE染色观察肝组织病理变化;Western blot检测肝脏中SHP、pFOXO1、pCREB、PEPCK、G6Pase蛋白表达量。结果与HFD组比较,E40组体质量降低,肝脏体积减小并呈健康暗红色;E40组与HFD组比较,肝指数、肝脏中脂代谢及肝功能指标降低;OGTT试验显示,E40组较HFD组葡萄糖耐量增强,曲线下面积降低;E40组较HFD组血清中血糖、胰岛素、甘油三酯、抵抗素、瘦素、胰高血糖素以及纤溶酶原激活物抑制剂-1水平降低;HE染色显示,HFD组较RD组肝细胞增大并伴有大泡性脂肪变性,E40组明显改善肝细胞脂肪变性及肝脏病理状态;Western blot结果表明,E40组与HFD组比较,肝脏中SHP、pFOXO1、pCREB蛋白表达上调,PEPCK、G6Pase蛋白表达下调。结论丁香酚可能通过调控SHP/pFOXO1/PCREB/PEPCK/G6Pase信号转导通路,调节肝脏糖脂代谢、抑制胰岛素抵抗,改善T2DM的血糖水平及肝脏糖脂代谢紊乱。Aim To study the effects of eugenol on hypoglycemic effect and hepatic glucose and lipid metabolism in type 2 diabetic mice,and to explore the possible mechanism.Methods The model of type 2 diabetes induced by long term high-fat diet was divided into four groups.The blood glucose and body weight of each group were measured once a week.After six weeks,the liver tissues of mice in each group were dissected and the liver mass and body mass of mice were weighed.Liver index,lipid metabolism and liver function were measured.Oral glucose tolerance test was performed.The levels of blood glucose,insulin,triglyceride,cholesterol,resistin,leptin,auxin,glucagon and plasminogen activator inhibitor-1 in serum were measured.He staining was used to observe the pathological changes of liver tissues.The expressions of SHP,pfoxo1,pCREB,PEPCK and G6Pase proteins in liver were detected by Western blot.Results Compared with HFD group,E40 group had lower body weight,smaller liver volume and healthy dark red.Compared with HFD group,E40 group decreased liver index,lipid metabolism and liver function.OGTT test showed that glucose tolerance was enhanced and the area under the curve was decreased in E40 group compared with HFD group.The levels of blood glucose,insulin,triglyceride,resistin,leptin,glucagon and plasminogen activator inhibitor-1 in E40 group were lower than those in HFD group.He staining showed that hepatocytes in HFD group were larger and accompanied with bullous steatosis than those in RD group.Hepatocyte steatosis and liver pathological state were significantly improved in E40 group.The results of Western blot showed that compared with HFD group,the expression of SHP,pfoxo1 and pCREB protein in E40 group was up-regulated,and the expression of PEPCK and G6Pase protein was down-regulated.Conclusions Eugenol can regulate the SHP/pFOXO1/PCREB/PEPCK/G6Pase signaling pathway,regulate glucose and lipid metabolism,inhibit insulin resistance,improve blood glucose level and glucose and lipid metabolism disorders in type 2 diabetes me

关 键 词：丁香酚 肝脏 糖脂代谢紊乱 胰岛素抵抗 2型糖尿病 信号通路 

分 类 号：R-332[医药卫生] R285.5R322.47R344.6R459.3R587.1