花生四烯酸对高脂饮食大鼠全身胰岛素抵抗及肝糖输出影响的研究

Effects of AA on whole-body insulin resistanc and hepatic glucose output in insulin-resistant rats induced by a high-fat diet

目的观察花生四烯酸对大鼠全身胰岛素抵抗及肝糖输出紊乱的预防作用。方法将230～250g24只雄性Wistar大鼠随机分为3组:正常组(8例),高脂组(8例),高脂+花生四烯酸组即预防组(8例)。饲养12周。饲养至第12周实验终点时进行口服葡萄糖耐受实验。断头处死各组处于空腹状态下的大鼠,取肝脏,蒽酮法测定肝糖原含量,并用RT-PCR法检测磷酸烯醇式丙酮酸羧激酶(PEPCK)、葡萄糖-6-磷酸酶(G-6-Pase)及糖原合酶(GS) mRNA水平。结果高脂组与正常对照组比较,肝糖原含量(P<0.01)、葡萄糖-胰岛素指数显著升高(P<0.01),但基础状态下体重差异无显著性。预防组和高脂组比较,肝糖原含量(P<0.05)、葡萄糖-胰岛素指数(P<0.01)显著降低,但与正常对照组比较,肝糖原含量(P<0.01)、葡萄糖-胰岛素指数(P<0.01)显著升高。高脂组与正常对照组比较,G-6-Pase mRNA水平显著升高(P<0.01),PEPCK mRNA水平略有升高,但差异无显著性。预防组和高脂组比较,PEPCK mRNA水平(P<0.05)、G-6-Pase mRNA水平显著降低(P<0.01),但3组大鼠GSmRNA差异没有显著性。结论花生四烯酸预防高脂诱导的全身胰岛素抵抗和肝糖输出紊乱作用明显,但不彻底。相关的PEPCK、G-6-Pase mRNA水平显著降低,但GS mRNA水平没有显著性差异。

【Objective】To investigate the effects of arachidonic acid（AA） on whole-body insulin resistance and hepatic glucose output（HGO） disturbance in insulin-resistant rats induced by a high-fat diet.【Methods】Twenty-four normal male wistar rats（230-250 g）were randomly divided into 3 groups：control group,n=8,to be fed standard chow diet for 12 weeks;high-fat（HF） group,n=8 to be fed with a high-fat diet for 12 weeks,AA＋HF group,n=8,to be fed with a high-fat diet and adiministered orally 3 mg.kg-1.d-1AA for 12 weeks.By the end of experiment,an oral glucose tolerance test were conducted.At the end of the experiment,the rats were sacrificed.Glycogen content in liver was measured using the anthrone method,phosphoenolpyruvate carboxykinase（PEPCK）,glucose-6-phosphatase（G-6-Pase） and glycogen synthase（GS） mRNA levels were quantified by RT-PCR.【Results】Early insulin resistance was successfully induced in HF rats with higher fasting liver glycogen content（P〈0.01） and higher glucose-insulin index（P〈0.01） during OGTT compared with control rats.The AA treatment significantly decreased glucose-insulin index（P〈0.01）,glycogen content（P〈0.05） in liver.Significantly decreased mRNA levels of PEPCK（P〈0.05〈） and G-6-Pase（P0.01） in liver were also observed.But there were significant differences in glucose-insulin index（P〈0.01） during OGTT,and glycogen content（P0.01） between HF＋AA group and control group.There were no significant differences in GS mRNA levels among the three groups.【Conclusions】 AA can significantly prevent HGO disturbance in rats with insulin resistance induced by a high-fat diet,as well as whole-body insulin resistance,but not thoroughly.The relative PEPCK and G-6-Pase mRNA levels were decreased significantly.