鞣花酸改善2型糖尿病小鼠脂肪组织胰岛素抵抗的实验研究

Experimental study of ellagic acid on the improving insulin resistance in adipose tissue of type 2 diabetic mice

目的研究多酚类化合物鞣花酸(EA)对糖尿病小鼠脂肪组织胰岛素抵抗的影响及机制。方法雄性C57BL/6小鼠高脂饲喂联合85 mg·kg^(-1)剂量链脲佐菌素腹腔注射建立2型糖尿病模型,另设普通饲料喂养的正常组。按照随机数字表法将造模成功小鼠分为2组:模型组和实验组,每组10只。继续给与高脂饲料喂养,同时实验组灌胃给予50 mg·kg^(-1)EA,正常组和模型组小鼠给与相应剂量蒸馏水灌胃。给药8周后,检测各组小鼠血脂水平,计算空腹胰岛素抵抗指数(FIRI);蛋白质印迹法检测脂肪组织胰岛素受体底物1(IRS-1)、磷酸化蛋白激酶B(p-Akt)和葡萄糖转运蛋白4(Glut-4)蛋白的表达。结果正常组、模型组和实验组的LDL-C水平分别为(2.53±0.23),(3.54±0.36)和(2.65±0.13)mmol·L^(-1);这3组的FIRI水平分别为1.85±0.07,9.33±1.84和4.89±1.06;这3组的IRS-1蛋白相对表达量分别为1.03±0.08,0.48±0.05和0.64±0.09;这3组的p-Akt蛋白相对表达量分别为0.99±0.06,0.24±0.08和0.47±0.07;这3组的Glut-4蛋白相对表达量分别为1.03±0.07,0.21±0.09和0.45±0.04。上述指标:模型组与正常组比较,或者实验组与模型组比较,差异均有统计学意义(均P<0.01)。结论EA可显著改善糖尿病小鼠血脂异常,纠正糖尿病小鼠脂肪组织胰岛素信号转导障碍。

Objective To study the effect and mechanism of polyphenols ellagic acid(EA)on insulin resistance in adipose tissue of diabetic mice.Methods Male C57 BL/6 mice were fed with high-fat diet combined with 85 mg·kg^(-1)dose of streptozotocin intraperitoneally to establish a type 2 diabetes model,and normal group fed with ordinary diet.The successfully modeled mice were divided into two groups according to random number table:model group and the experimental group(50 mg·kg^(-1)dose of ellagic acid),10 mice in each group;continue to feed on high-fat diet.The corresponding dose of distilled water was given by gavage in model group and normal group.After 8 weeks of administration,the blood lipid level was detected,and the fasting insulin resistance index(FIRI)was calculated.The expressions of insulin receptor substrate 1(IRS-1),phosphorylated protein kinase B(p-Akt),glucose transporter 4(Glut-4)in adipose tissue were detected by Western blotting.Results The LDL-C levels in normal group,model group and experimental group were(2.53±0.23),(3.54±0.36)and(2.65±0.13)mmol·L-1;the FIRI levels in the three groups were 1.85±0.07,9.33±1.84 and 4.89±1.06;the relative expression levels of IRS-1 protein in the three groups were 1.03±0.08,0.48±0.05 and 0.64±0.09;the relative expression of p-Akt protein in the three groups were 0.99±0.06,0.24±0.08 and 0.47±0.07;the relative expression of Glut-4 protein in the three groups were 1.03±0.07,0.21±0.09 and 0.45±0.04.There were significant differences of the factors between model group and normal group or experimental group and model group(all P<0.01).Conclusion EA can significantly improve dyslipidemia,and insulin signal transduction disorder in adipose tissue of diabetic mice.