双(α-呋喃甲酸)氧钒与二甲双胍联用对糖尿病模型小鼠的降糖作用研究

Hypoglycemic Effect of Bis(α-furancarboxylato)oxovanadium Combined with Metformin on Diabetic Mice

目的:研究双(α-呋喃甲酸)氧钒(BFOV)与二甲双胍联用对糖尿病模型小鼠的降糖作用。方法:取小鼠尾静脉注射四氧嘧啶建立糖尿病模型后,随机分为模型组、BFOV(18 mg/kg)组、二甲双胍(125 mg/kg)组及联用组,另取正常小鼠作为正常对照组,每组10只;除正常对照组和模型组小鼠灌胃生理盐水外,其余各组小鼠灌胃相应药物,每日1次,连续4周。给药期间,每周检测各组小鼠给药1 h后的非空腹血糖水平,给药结束后取各组小鼠肝脏和肌肉,检测其肝糖原、肌糖原、游离脂肪酸(FFA)、甘油三酯(TG)、总胆固醇(CHO)、己糖激酶(HK)、腺苷酸活化蛋白激酶(AMPK)水平。结果:与正常对照组比较,其余各组小鼠给药期间的非空腹血糖水平均明显升高(P<0.01),除联用组外其余各组小鼠的肝糖原、肌糖原均明显降低(P<0.05);模型组和BFOV组小鼠的FFA、CHO均明显升高(P<0.05),仅模型组小鼠的TG明显升高(P<0.05);BFOV组和联用组小鼠的HK明显升高(P<0.05)。与模型组比较,联用组小鼠给药2周后非空腹血糖水平、FFA、TG、CHO均明显降低(P<0.05),肝糖原、肌糖原均明显升高(P<0.05);BFOV组和联用组小鼠的HK均明显升高(P<0.05);BFOV组、二甲双胍组及联用组小鼠的p AMPK/t AMPK均明显升高(P<0.05),其中联用组小鼠的HK和p AMPK/t AMPK升高更明显(P<0.05),其余各组差异无统计学意义(P>0.05)。结论:BFOV与二甲双胍联用对糖尿病模型小鼠糖脂代谢紊乱具有协同改善作用,其作用机制可能与激活AMPK有关。

OBJECTIVE： To study hypoglycemic effect of bis （a-furancarboxylato）oxovanadium （BFOV） combined with met- formin on diabetic mice. METHODS： Mice was given alloxan via tail vein to induce diabetic model, and then randomly divided in- to model group, BFOV group （18 mg/kg） , metformin group （125 mg/kg） and drug combination group with 10 mice in each group. 10 healthy mice were included in normal control group. Normal control group and model group were given normal saline, while other groups were given relevant medicines intragastrically once a day for consecutive 4 weeks. Postprandial blood glucose of mice was determined 1 h after medication every week during treatment. Liver tissue and muscle of mice were sampled at the end of medication. The levels of liver glycogen, muscle glycogen, free fatty acid （FFA）, triglyceride （TG）, total cholesterol （CHO）, hexokinase （HK） and 5-AMP activated protein kinase （AMPK） were determined. RESULTS. Compared with normal control group, postprandial blood glucose of mice were increased significantly in other groups （P〈0.01）, and the glycogen content of he- patic and skeletal muscle were decreased significantly in those groups except for drug combination group （P〈0.05） ; the levels of FFA and CHO in model group and BFOV group were increased significantly （P〈0.05） ; TG of model group was increased signifi- cantly （P〈0.05） ; HK of BFOV group and drug combination group were increased significantly （P〈0.05）. Compared with model group, postprandial blood glucose, FFA, TG and CHO of drug combination group were decreased significantly 2 weeks after medi- cation （P〈0.05）, while the glycogen content of hepatic and skeletal muscle were increased significantly （P〈0.05） ; HK of BFOV group and drug combination group both were increased significantly （P〈0.05） ; pAMPK/tAMPK of BFOV group, metformin group and drug combination group were all increased significantly （P〈0.05） ; the increase of HK and pAMPK/tAMPK were more significant in drug combination group （P〈0.05） ; there was no statistical significance among other groups（P〉0.05）. CONCLU- SIONS： BFOV combined with metformin has synergic effect on glucose and lipid metabolism disorder in diabetic model mice, and its mechanism may be associated with the activation of AMPK.