首页|基于AMPK通路探讨茶多酚改善糖尿病大鼠糖脂代谢机制

基于AMPK通路探讨茶多酚改善糖尿病大鼠糖脂代谢机制

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目的:探讨茶多酚从AMP活化蛋白激酶(AMPK)通路途径调控糖尿病大鼠糖脂代谢的机制.方法:经糖耐量试验筛选6周龄SD大鼠45只,按随机数字表法分为正常组10只和造模组35只,造模组糖尿病造模成功后剩余30只,根据体质量分层法和血糖水平分为模型组、二甲双胍组和茶多酚组,每组各10只.各组均于每日下午灌胃,正常组与模型组给予无菌生理盐水,二甲双胍组给予二甲双胍水溶液,茶多酚组给予茶多酚.干预120 d后,检测各组大鼠的空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C);酶联免疫吸附试验法检测肝脏乙酰辅酶A羧化酶(ACC)和激素敏感性脂肪酶(HSL);实时荧光定量法检测肝脏ACC mRNA、转录因子胆固醇调节元件结合蛋白1(SREBP-1)mRNA、3-羟基-3-甲基戊二酸单酰辅酶A还原酶(HMGCR)mRNA;免疫印迹法检测肝脏AMPKα1、磷酸化AMP活化蛋白激酶α1(P-AMPKα1)、SREBP1、HMGCR、肉毒碱棕榈酰转移酶1(CPT1)、葡萄糖转运蛋白4(GLUT4)和磷酸烯醇丙酮酸羧化激酶(PEPCK).结果:与正常组比较,模型组大鼠的一般情况较差,FBG、TG、TC、LDL-C、ACC 升高(P<0.05),SREBP1、HMGCR 蛋白及mRNA表达升高(P<0.05),CPTI、PEPCK 蛋白表达升高(P<0.05),HDL-C、HSL 降低(P<0.05),AMPKα 1、P-AMPKα 1、GLUT4 蛋白表达降低(P<0.05).与模型组比较,茶多酚组大鼠的一般情况改善,TG、LDL-C、ACC降低(P<0.05),SREBP1、HMGCR蛋白及mRNA表达降低(P<0.05),PEPCK 蛋白表达降低(P<0.05),HDL-C、HSL 升高(P<0.05),AMPKα1、P-AMPKα1、GLUT4、CPT1蛋白表达升高(P<0.05).与二甲双胍组比较,茶多酚组TC升高(P<0.05),FBG、TG、LDL-C、HDL-C、HSL、ACC、ACC mRNA、HMGCR mRNA、SREBP1 mRNA、AMPKα1、P-AMPKα1、SREBP1、HMGCR、CPT1、GLUT4、PEPCK相对表达量差异无统计学意义(P>0.05).结论:茶多酚可能通过调节AMPK通路,影响HSL、HMGCR、SREBP1、CPTI、GLUT4和PEPCK,从而改善糖尿病大鼠糖脂代谢.
Mechanism of Tea Polyphenols in Improving Glucose and Lipid Metabolism in Diabetic Rats Based on AMPK Pathway
Objective:To explore how tea polyphenols regulate glucose and lipid metabolism in diabetic rats through the AMP-activated protein kinase(AMPK)pathway.Methods:Total 45 six-week-old SD rats were screened by the glucose tolerance test and divided into the normal group of 10 rats and the model group of 35 rats according to the random number table method.After successfully establishing the diabetic model,the remaining 30 rats were stratified by body weight and blood glucose levels into the model group,the metformin group,and the tea polyphenol group,with 10 rats in each group.Each group was gavaged every afternoon:the normal and model groups received sterile saline,the metformin group received metformin solution,and the tea polyphenol group received tea polyphenols.After 120 days of intervention,fasting blood glucose(FBG),total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were measured in each group.Enzyme linked immunosorbent assay was used to detect liver acetyl-CoA carboxylase(ACC)and hormone-sensitive lipase(HSL).Real-time fluorescence quantification was used to detect liver ACC mRNA,transcription factor sterol regulatory element-binding protein 1(SREBP-1)mRNA,3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR)mRNA.Western blotting was used to detect liver AMPKα1,P-AMPKα1,SREBP1,HMGCR,carnitine palmitoyltransferase 1(CPT1),glucose transporter 4(GLUT4),and phosphoenolpyruvate carboxykinase(PEPCK).Results:Compared with the normal group,the general condition of rats in the model group was poor,FBG,TG,TC,LDL-C,ACC were increased(P<0.05),SREBP1,HMGCR protein,and mRNA expression were increased(P<0.05),CPTI,PEPCK protein expression were increased(P<0.05),HDL-C,HSL were decreased(P<0.05),AMPKα1,P-AMPKα1,GLUT4 protein expression were decreased(P<0.05).Compared with the model group,the general condition of rats in the tea polyphenol group improved,TG,LDL-C,ACC were decreased(P<0.05),SREBP1,HMGCR protein and mRNA expression were decreased(P<0.05),PEPCK protein expression was decreased(P<0.05),HDL-C,HSL were increased(P<0.05),AMPKα1,P-AMPKα1,GLUT4,CPT1 protein expression were increased(P<0.05).Compared with the metformin group,the tea polyphenol group showed an increase in TC(P<0.05),with no statistical significance in the relative expression of FBG,TG,LDL-C,HDL-C,HSL,ACC,ACC mRNA,HMGCR mRNA,SREBP1 mRNA,AMPKα1,P-AMPKα1,SREBP1,HMGCR,CPT1,GLUT4,PEPCK(P>0.05).Conclusion:Tea polyphenols may improve glucose and lipid metabolism in diabetic rats by regulating the AMPK pathway,affecting HSL,HMGCR,SREBP1,CPTI,GLUT4,and PEPCK.

diabetestea polyphenolsmetforminAMP-activated protein kinase pathwayglucose and lipid metabolismrat

黄苏萍、林欢、曾淑华、杨柳媛、许陆达

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福建中医药大学,福建福州 350122

糖尿病 茶多酚 二甲双胍 AMP活化蛋白激酶通路 糖脂代谢 大鼠

国家自然科学基金面上项目福建省医疗创新项目

82071512082018-CX-41

2024

山东中医药大学学报
山东中医药大学

山东中医药大学学报

CSTPCD
影响因子:0.52
ISSN:1007-659X
年,卷(期):2024.48(2)
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