AMPK活化对慢性间歇缺氧大鼠胰岛素抵抗和炎症因子的影响

Effects of AMPK activation on insulin resistance and inflammatory factors in rats with chronic intermittent hypoxia

目的探讨单磷酸腺苷激活蛋白激酶(AMPK)活化对慢性间歇缺氧大鼠胰岛素抵抗和炎症因子的作用及其机制。方法建立慢性间歇缺氧大鼠模型模拟阻塞性睡眠呼吸暂停综合征(OSAS),将36只雄性SD大鼠分为常氧对照组、2周间歇缺氧组、8周间歇缺氧组。观察AMPK激动剂和AMPK抑制剂作用不同缺氧程度的大鼠体内炎症介质、血脂、脂联素、瘦素及胰岛素抵抗水平,监测大鼠脂肪组织AMPK、葡萄糖转运蛋白(GLUT4)水平,并进行统计学分析。结果间歇缺氧大鼠总胆固醇、三酰甘油、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-2、核因子κB(NF-κB)、缺氧诱导因子(HIF-1)显著高于对照组(P<0.05);脂联素、瘦素及胰岛素抵抗指数显著低于对照组(P<0.05)。使用AMPK激活剂后的大鼠体内炎症因子释放减少,脂联素、瘦素含量增加,血脂、胰岛素抵抗情况较前有改善,GLUT4水平增加。而使用AMPK抑制剂处理后大鼠体内炎症因子、脂联素、瘦素水平均上升,胰岛素抵抗更严重,GLUT4水平也进一步下降。结论 AMPK能够减少炎症介质的释放,促进脂联素、瘦素的释放,增加GLUT4水平,改善胰岛素抵抗,从而调节能量代谢及炎症介质,为临床治疗OSAS相关疾病提供新的思路与靶点。

Objective To investigate the effect and mechanism of adenosine monophosphate activated protein kinase（AMPK） activation on insulin resistance and inflammatory factors in rats with chronic intermittent hypoxia. Methods The chronic intermit- tent hypoxia rat model was established to simulate the obstructive sleep apnea syndrome （OSAS）, and the 36 male SD rats were di- vided into the normal oxygen control group, 2-week intermittent hypoxia group and 8-week intermittent hypoxia group. The levels of rat inflammatory medium, serum lipid,adiponectin, leptin and insulin resistance in different hypoxia degrees of rats by the action of AMPK agonist and AMPK inhibitor were observed,and the levels of AMPK and GLUT4 in rat adipose tissue were monitored and statistically analyzed. Results The levels of total cholesterol,triglyceride,TNF-α,IL-6,IL-2,NF-κB and HIF-1 in the intermittent hypoxia rats were significantly higher than those in the control group（P〈0.05）;while the levels of adiponectin,leptin and insulin resistance index were significantly lower than those in the control group（P〈0.05）. The release of inflammatory factors in rats after using AMPK activator was decreased,the contents of adiponectin and leptin were increased,blood lipid and insulin resistance were improved compared with before,and the expression level of GLUT4 was increased. But after treatment by using AMPK inhibitor, the levels of inflammatory factors, adiponectin and leptin were increased,insulin resistance was more severe, and the expression level of GLUT4 protein was also further decreased. Conclusion AMPK can reduce the release of inflammatory mediators,promotes the release of adiponectin and leptin, increases the level of GLUT4,improves insulin resistance, thus regulates the energy metabolism and inflammatory mediators,which provides a new idea and target for clinical treatment of OSAS related diseases.