奥贝胆酸对2型糖尿病KKAy小鼠的糖脂稳态影响  

Effect of obeticholic acid on glycolipid homeostasis in type 2 diabetic KKAy mice

作　　者：曹慧 环奕[1] 李彩娜[1] 刘率男[1] 刘泉[1] 孙素娟[1] 雷蕾[1] 申竹芳[1] CAO Hui;HUAN Yi;LI Cai-na;LIU Shuai-nan;LIU Quan;SUN Su-juan;LEI Lei;SHEN Zhu-fang(Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Diabetes Research Center of Chinese Academy of Medical Sciences,Beijing 100050,China)

机构地区：[1]中国医学科学院北京协和医学院药物研究所,天然活性物质与功能国家重点实验室,中国医学科学院糖尿病研究中心,北京100050

出　　处：《中国新药杂志》2021年第4期352-356,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(81900480);北京市自然科学基金资助项目(7204281)。

摘　　要：目的:研究奥贝胆酸(obeticholic acid,OCA)对自发性2型糖尿病KKAy小鼠的抗糖尿病作用。方法:将KKAy小鼠随机分为对照组(Control)和奥贝胆酸组(OCA,10 mg·kg^(-1)),每组9只,ig给药,qd,连续6周。实验期间检测小鼠的体重、摄食量、摄水量、血糖、血脂、糖化血红蛋白和胰岛素水平,计算胰岛素抵抗指数,并进行口服葡萄糖耐量实验和胰岛素耐受实验。实验结束后,记录小鼠肝重量,计算肝系数,检测小鼠肝脂质含量,采用HE染色观察肝脂质变性程度。结果:OCA可明显降低KKAy小鼠的体重、随机血糖、空腹血糖、糖化血红蛋白及血胰岛素水平,改善葡萄糖耐受性和胰岛素敏感性;显著降低小鼠肝系数及血清和肝组织中三酰甘油的含量。结论:OCA可改善2型糖尿病KKAy小鼠的糖脂代谢紊乱、减轻胰岛素抵抗,发挥有效的抗糖尿病作用。Objective: To explore the antidiabetic effects of obeticholic acid( OCA) in spontaneous type 2 diabetic KKAy mice. Methods: KKAy mice were randomly divided into two groups: control group( Control) and obeticholic acid-treated group( OCA,10 mg·kg^(-1)). Nine mice in each group were administered by gavage once daily for 6 weeks. The body weight,food consumption,water consumption,glycemia,lipidemia,glycated hemoglobin,and insulin levels were monitored,the index of insulin resistance was calculated,and oral glucose tolerance test( OGTT) and insulin tolerance test( ITT) were performed. Liver weight and its index,and lipid contents in liver tissues were measured;lipid degeneration of liver was evaluated by HE staining. Results: OCA obviously lowered body weight and levels of non-fasting blood glucose,fasting blood glucose,insulin,and HbA1c,and improved glucose tolerance as well as insulin sensitivity. Additionally,OCA decreased liver weight,liver coefficient,and contents of triglyceride in serum and liver of KKAy mice. Conclusion: OCA exhibits beneficial anti-diabetic effects in type 2 diabetic KKAy mice through improving glucolipid metabolism disorder and ameliorating insulin resistance.

关 键 词：奥贝胆酸 2型糖尿病 糖脂代谢 胰岛素抵抗 

分 类 号：R965[医药卫生—药理学]