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目的探讨2型糖尿病大鼠心肌葡萄糖转运体4(GLUT4)的表达与葡萄糖及其脂肪酸氧化代谢的关系,同时观察罗格列酮使用后上述指标的变化。方法24只SD雄性大鼠随机分为实验治疗组(6只)、实验对照组(6只)、正常治疗组(6只)和正常对照组(6只)。采用高脂喂养(40%脂肪、42%碳水化合物和18%蛋白质)4周及小剂量链脲佐菌素(35mg/kg)一次性腹腔注射建立2型糖尿病大鼠模型。实验治疗组和正常治疗组给予罗格列酮3mg·kg-1·d-1灌胃2周;各组大鼠进行30min等容离体心脏Langendorff灌注,灌注液含100μU胰岛素、5mmol/L葡萄糖、0.4mmol/L3H软脂酸,测定样本葡萄糖含量及3H2O计数,评估心肌葡萄糖和脂肪酸氧化率;Western印迹法检测心肌细胞膜GLUT4表达水平。结果与正常对照组比较,实验对照组大鼠心肌葡萄糖总氧化量明显较少[(55±6)μmol/g干重vs(69±6)μmol/g干重,P<0.01],葡萄糖氧化比例较少(18%vs25%),脂肪酸氧化率较高(82%vs75%);同时心肌细胞膜上GLUT4的表达量减少53%。与实验对照组比较,给予RSG的实验治疗组,心肌葡萄糖的氧化量较高为(64±6)μmol/g干重(P<0.05),葡萄糖和脂肪酸的氧化比例分别为24%和76%,GLUT4表达量也明显较大(92%vs47%,P<0.01)。结论心肌细胞膜上GLUT4表达减少可能是2型糖尿病心肌葡萄糖和脂肪酸氧化代谢改变的重要原因,罗格列酮通过增加GLUT4的表达,可以提高心肌葡萄糖氧化、降低脂肪酸氧化,这将有助于减轻糖尿病心肌细胞损伤,增强抗缺血的能力。
Objective To investigate the relationship between the expression of glucose transporter 4 (GLUT4) and the glucose and fatty acid oxidative metabolism in type 2 diabetic rats and to observe the changes of these indexes after the administration of rosiglitazone. Methods Twenty-four SD male rats were randomly divided into experimental treatment group (n = 6), experimental control group (n = 6), normal treatment group (n = 6) and normal control group (n = 6). Type 2 diabetic rat models were established by intraperitoneal injection of high-fat diet (40% fat, 42% carbohydrates and 18% protein) for 4 weeks and low-dose streptozotocin (35 mg / kg) Rats in experimental group and normal treatment group were given Rosiglitazone 3 mg · kg-1 · d-1 for 2 weeks. Rats in each group were given Langendorff perfusion with isokinetic Langendorff in 30 minutes. The perfusion solution contained 100 μU insulin and 5 mmol / L glucose , 0.4 mmol / L H3 palmitate. The content of glucose and 3H2O in the samples were measured to evaluate the myocardial glucose and fatty acid oxidation rate. The expression of GLUT4 in the myocardial cell membrane was detected by Western blotting. Results Compared with the normal control group, the total myocardial glucose oxidation in the experimental control group was significantly less than that in the control group [(55 ± 6) μmol / g dry weight vs 69 ± 6 μmol / g dry weight, P <0.01] (18% vs 25%), higher fatty acid oxidation rate (82% vs 75%), and a 53% decrease in the expression of GLUT4 on the myocardial cell membrane. Compared with the experimental control group, the experimental group treated with RSG had a higher oxidation of myocardial glucose (64 ± 6) μmol / g dry weight (P <0.05), and the glucose and fatty acid oxidation rates were 24% and 76% , GLUT4 expression was also significantly larger (92% vs47%, P <0.01). Conclusions The decrease of GLUT4 expression in myocardial cell membrane may be an important reason for the oxidative metabolism of glucose and fatty acid in type 2 diabetes mellitus. Rosiglitazone can increase myocardial glucose oxidation and decrease fatty acid oxidation by increasing the expression of GLUT4, which will help to reduce diabetes mellitus Myocardial cell injury, enhanced anti-ischemic ability.