吡格列酮对高脂喂养大鼠骨骼肌组织脂质异位沉积的影响

Effects of pioglitazone on ectopic lipid accumulation in skeletal muscles in rats fed with high fat diet

目的:观察吡格列酮(Pio)对高脂喂养大鼠骨骼肌组织脂质异位沉积的影响。方法:30只Wistar大鼠平均分为对照组、胰岛素抵抗组和吡格列酮干预组,对照组给予基础饲料,其余2组均给予高脂饲料喂养,其中吡格列酮干预组同时给予吡格列酮20 mg·kg-1·d-1灌胃,各组均喂养16周后检测各组大鼠血游离脂肪酸(FFA)水平及骨骼肌组织中三酰甘油(TG)含量,同时应用蛋白免疫印迹法检测骨骼肌组织一磷酸腺苷活化蛋白激酶α(AMPKα)磷酸化水平。结果:与对照组比较,胰岛素抵抗组大鼠胰岛素敏感性显著降低,血FFA水平及骨骼肌组织TG含量增高,骨骼肌组织中AMPKα磷酸化水平降至对照组水平的52.9%;与胰岛素抵抗组比较,吡格列酮干预组大鼠胰岛素敏感性明显提高,血FFA水平及骨骼肌组织TG含量显著下降,骨骼肌组织中AMPKα磷酸化水平显著提高至对照组的81.3%。但是与对照组比较,吡格列酮干预组大鼠血FFA水平及骨骼肌组织TG含量仍然较高,而且胰岛素敏感性及骨骼肌组织中AMPKα磷酸化水平仍然显著降低。结论:高脂饮食诱导胰岛素抵抗,吡格列酮干预可以通过降低血FFA水平及减轻骨骼肌组织脂质异位沉积改善其胰岛素抵抗。

OBJECTIVE To observe the effects of pioglitazone on ectopic lipid accumulation in skeletal muscles in rats fed with high fat diet.METHODS Thirty Wistar rats were randomly allocated to three groups（10 rats for each group）：normal control group（NC group,fed with standard chow）,insulin resistance group（IR group,fed with high fat diet）and pioglitazone group（PT group,fed with high fat diet）.Rats in pioglitazone group received pioglitazone（20 mg·kg^-1·d^-1）.After 16 weeks,all rats were sacrificed.The insulin sensitivity index was calculated.Serum free fatty acid（FFA）and triglyceride content in skeletal muscles was detected.Phosphorylation of AMPKαlevel in skeletal muscles was detected by Western blot.RESULTSSixteen weeks later,compared to NC group,insulin sensitivity index（ISI）of IR group significantly decreased,while serum FFA level and triglyceride content in skeletal muscles both increased.Phosphorylation of AMPKαlevel in IR group decreased to52.9% of NC group.Compared to IR group,ISI evidently improved,serum FFA level and triglyceride content in skeletal muscles were lower,and phosphorylated AMPKαelevated to 81.3% of NC group in PT group.However,compared to NC group,serum FFA level and triglyceride content in skeletal muscles were still relatively high in PT group,while incise and phosphorylated AMPKαstill significantly low.CONCLUSION Pioglitazone can markedly alleviate insulin resistance induced by high fat diet through decreasing serum FFA level and reducing ectopic lipid accumulation in skeletal muscles.