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[摘要]
目的 研究绿原酸对高脂饲喂SD大鼠骨骼肌糖代谢的调节机制。方法 40只雄性SD大鼠随机分成5组:对照组、模型组,低、高剂量(20、90 mg/kg)绿原酸组,罗格列酮(阳性对照)组,其中对照组饲喂普通饲料,其余各组大鼠饲喂高脂饲料。给药12周后处死大鼠,取骨骼肌,用实时荧光定量-PCR方法测定骨骼肌糖代谢过程中相关基因蛋白激酶B(PKB,又名Akt)、磷脂酰肌醇-3激酶(PI3K)、胰岛素受体底物-1(IRS-1)、葡萄糖转运蛋白4(GLUT-4)、蛋白激酶A(PKA)、AMP依赖的蛋白激酶(AMPK-α2)、过氧化物酶体增殖物激活受体(PPARα、PPARβ、PPARγ)的表达。结果 与对照组比较,模型组大鼠骨骼肌中GLUT-4、AMPK-α2和PPARβ mRNA表达量显著下降(P< 0.05、0.01);与模型组相比,绿原酸干预能提高糖代谢途径中相关基因的表达,其中绿原酸高剂量组Akt、PI3K、IRS-1、GLUT-4、PKA、AMPK-α2、PPARα、PPARβ mRNA的表达量显著上调(P< 0.05、0.01)。结论 高剂量绿原酸能显著减缓高脂饲喂SD大鼠体质量增加,并通过调节PI3K/Akt途径、AMPK途径和胰岛素敏感性,改善骨骼肌中糖代谢。
[Key word]
[Abstract]
Objective To investigate the mechanisms of chlorogenic acid (CGA) on regulating carbohydrate metabolism in skeletal muscle of SD rats fed on high-fat diet. Methods Forty male SD rats were randomly divided into five groups: normal control (NC), high-fat diet (HFD), HFD with low-dose-CGA (20 mg/kg, HFD-LC), HFD with high-dose-CGA (90 mg/kg, HFD-HC), and Rosiglitazone (HFD-ROS) groups. NC rats were fed with normal chow diet, while the other rats were fed with HFD. The rats were killed after 12 weeks, and the real-time PCR method was used to measure the expression levels of GLUT-4, PKA, Akt, AMPKα2, IRS-1, PI3K, and PPARs mRNA in skeletal muscle. Results The expression levels of GLUT-4, AMPKα2, and PPARβ in HFD group were more dramatically decreased than those in the NC group (P < 0.05); Compared with the HFD group, CGA increased genes involved in carbohydrate metabolism, particularly Akt, PI3K, IRS-1, GLUT-4, PKA, AMPKα2, PPARα, and PPARβ in HFD-HC group (P < 0.05). Conclusion High-dose CGA could significantly slow the weight gain induced by HFD, as well as improve carbohydrate metabolism in skeletal muscle through regulating PI3K/Akt and AMPK signaling pathways, and insulin sensitivity.
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[基金项目]
国家自然科学基金资助项目(31071531);湖南省教育厅重点项目(14A071)