AMPK对大鼠OSAS模型所致胰岛素抵抗的影响

Effects of AMPK on insulin resistance induced by OSAS model in rats

目的探讨激活及抑制腺苷酸活化蛋白激酶(AMPK)对阻塞性睡眠呼吸暂停综合征(OSAS)所致胰岛素抵抗、血脂水平变化以及炎症介质释放的影响。方法选取SPF级健康雄性SD大鼠16只,随机分为对照组、OSAS组、OSAS+激动剂组、OSAS+抑制剂组4组,每组各4只,对照组无处理,对其余3组构建OSAS模型。观察AMPK激动剂AICAR和抑制剂即AMPKα2shRNA质粒对甘油三酯、总胆固醇、空腹血糖、胰岛素抵抗指标HOMA-IR、脂联素、瘦素,以及炎症因子TNF-α、IL-6的影响。结果 OSAS模型大鼠的甘油三酯、总胆固醇、空腹血糖、HOMA-IR、TNF-α、IL-6水平均显著高于对照组,而脂联素、瘦素水平均显著低于对照组(所有P<0.05)。给予AICAR后,甘油三酯、总胆固醇、空腹血糖、HOMA-IR水平均显著下降,脂联素、瘦素水平均显著升高,炎症因子TNF-α、IL-6水平均显著下降(所有P<0.05)。而给予AMPKα2shRNA质粒后,则有相反的效果,导致了以上指标的恶化(P<0.05)。结论 AMPK能缓解OSAS模型大鼠引起的胰岛素抵抗,降低血脂水平,并减少炎症介质的释放。

Objective To investigate the effects of activation and inhibition of AMP-active protein kinase(AMPK on insulin resistance,blood lipid levels and inflammatory mediators release in patients with obstructive sleep apnea syndrome(OSAS).Methods The OSAS model of rats was constructed.The rats were divided into control group,OSAS group,OSAS+agonist group and OSAS+inhibitor group.The effects of AICAR as AMPK agonist and AMPKα2 shRNA plasmid as AMPK inhibitor on triglyceride,total cholesterol,fasting blood glucose,insulin resistance index HOMA-IR,adiponectin,leptin,and inflammatory factor TNF-αand IL-6 were observed.Results The triglyceride,total cholesterol,fasting blood glucose,HOMA-IR,TNF-α,IL-6 levels in OSAS rats were significantly higher than those in the control group,while adiponectin and leptin levels were significantly lower than those in the control group(all P<0.05).After giving AICAR,the triglycerides,total cholesterol,fasting blood glucose and HOMA-IR levels were significantly decreased,adiponectin and leptin levels were significantly increased,inflammatory factors TNF-αand IL-6 levels were significantly decreased(all P<0.05).After the AMPKα2 shRNA plasmid was given,the effects were reversed,resulting in the deterioration of the above indexes(all P<0.05).Conclusion AMPK can relieve insulin resistance in OSAS model rats,reduce blood lipid level,and reduce the release of inflammatory mediators.