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目的探讨罗格列酮(RGZ)对老年胰岛素抵抗(IR)大鼠肝脏脂肪酸代谢和腺苷酸活化蛋白激酶(AMPK)α表达及活性的影响。方法 22~24月龄雄性wistar大鼠随机分为老年对照(OC)组和高脂喂养组。4周后高脂喂养组IR状态形成,再随机分为高脂(HF)组和RGZ干预(RGZ)组,RGZ组予RGZ 3mg·kg~(-1)·d~(-1)灌胃,继续喂养4周。测定肝脏TG和AMPKα1、AMPKα2 mRNA表达,以及AMPKα1、AMPKα2、P-AMPKα蛋白表达。结果 (1)HF组FPG、FIns、FFA、TC和TG高于OC组;而RGZ干预后这些指标均下降;葡萄糖输注率HF组低于OC组,RGZ组高于HF组(P<0.05或P<0.01)。(2)肝脏TG HF组高于OC组,RGZ组低于HF组(P<0.01)。(3)肝脏AMPKα1、AMPKα2mRNA表达和蛋白表达三组间无统计学差异(P>0.05);肝脏P-AMPKα蛋白表达HF组低于OC组,RGZ组高于HF组(P<0.05或P<0.01)。结论高脂饮食导致老年大鼠肝脏脂肪酸代谢异常及IR;RGZ干预后AMPKa活性增加和肝脏脂质堆积减少,IR改善。
Objective To investigate the effects of rosiglitazone (RGZ) on hepatic fatty acid metabolism and AMPK expression in senile insulin resistance (IR) rats. Methods Male wistar rats aged 22 to 24 months were randomly divided into the old control group (OC) and the high fat diet group. After 4 weeks, the IR state of high fat diet group was formed and then randomly divided into high fat (HF) group and RGZ group (RGZ). RGZ group was administrated with RGZ 3 mg · kg -1 · d -1 , Continue feeding for 4 weeks. The liver TG and AMPKα1, AMPKα2 mRNA expression, as well as AMPKα1, AMPKα2, P-AMPKα protein expression. Results: (1) FPG, FIns, FFA, TC and TG in HF group were higher than those in OC group, while those in RGZ group were lower than those in OC group. Glucose infusion rate was lower in HF group than in OC group and RGZ group (P <0.05) Or P <0.01). (2) Liver TG HF group was higher than OC group, RGZ group was lower than HF group (P <0.01). (3) There was no significant difference in the expression of AMPKα1, AMPKα2 mRNA and protein between the three groups (P> 0.05); the expression of P-AMPKα protein in HF group was lower than that in OC group and RGZ group (P <0.05 or P < 0.01). Conclusion High-fat diet leads to liver fatty acid metabolism and IR in aged rats. AMPKa activity and hepatic lipid accumulation decrease after RGZ intervention, and IR improves.