甘草酸调控AMPK/ACC/SREBP信号通路改善胰岛素抵抗的机制

Effect of glycyrrhizic acid on insulin resistance by regulating AMPK/ACC/SREBP signaling pathway

为了观察甘草酸对胰岛素抵抗的作用,探究其可能的机制,将50只C57BL/6J雄性小鼠随机分成正常组、模型组、甘草酸高剂量组、甘草酸低剂量组和二甲双胍组,每组10只。除正常组外,其余小鼠采用长期高脂饮食法,复制胰岛素抵抗模型,并给予相应药物进行干预。采用全自动生化仪测定小鼠血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C);检测小鼠血糖和胰岛素的水平,观察其糖耐量和胰岛素耐量变化;Western blotting法检测肝脏腺苷酸活化蛋白激酶(AMPK)、磷酸化乙酰辅酸A羟化酶(ACC)和固醇调节元件结合蛋白(SREBP)的表达。结果表明:长期高脂饮食的小鼠TC、TG和LDL-C明显升高,空腹血糖、血清胰岛素水平均明显升高,糖耐量和胰岛素耐量出现异常,肝脏AMPK和ACC的磷酸化水平和SREBP表达下降,与正常组小鼠相比,具有极显著性差异(P<0.01)。经药物干预后,甘草酸高、低剂量组和二甲双胍组小鼠体质量下降,TC、TG和LDL-C明显降低,空腹血糖和血清胰岛素降低,糖耐量和胰岛素耐量异常得到改善,AMPK和ACC的磷酸化水平和SREBP表达升高,与模型组小鼠相比,具有显著性差异(P<0.01,P<0.05)。因此,本研究表明:甘草酸能够改善长期高脂饮食诱导的胰岛素抵抗,其机制可能与其调节肝脏AMPK/ACC/SREBP通路有关。

To investigate the effect of glycyrrhizic acid(GA)on insulin resistance in mice,50 male C57BL/6J mice were randomly divided into control group,model group,GA 100(100 mg/kg)group,GA 50(50 mg/kg)group and Metformin group respectively.Mice,except the control group,were given high-fat diet to establish the model of insulin resistance(IR).After treatment,mice were subjected for glucose and insulin tolerance test including the levels of TG,TC,HDL-C,LDL-C,aspartate aminotransferase,alanine transaminase,creatine kinase in the serum isolated from the animals by using automatic biochemical analyzer.The expressions of AMPK,ACC and SREBP in liver were examined by Western blotting.The levels of TG,TC,LDL-C were increased;the glucose intolerance and insulin intolerance induced by high fat diet,increased fasting blood glucose,serum insulin level;AMPK,ACC and SREBP phosphorylation levels were decreased(P<0.01).Compared with the HF group,GA significantly decreased body weight,TG,TC,LDL-C,significantly improved the glucose intolerance and insulin intolerance induced by high fat diet;improved the AMPK,ACC and SREBP phosphorylation level(P<0.01,P<0.05).