中文摘要：

目的研究新型褪黑素（MLT）受体激动剂Neu-P11对睡眠限制大鼠胰岛素敏感性的影响及其作用机制。方法采用转笼法对SD大鼠进行8天的睡眠限制,期间每天分别给予腹腔注射Neu-P11（20 mg/kg）、MLT（5mg/kg）、生理盐水。实验末测定空腹血糖、胰岛素、丙二醛（MDA）水平及GSH-Px、SOD活性,检测骨骼肌组织JNK及其磷酸化水平。结果与正常对照组比较,睡眠限制大鼠空腹血糖、胰岛素、HOMA-IR及MDA水平明显升高,SOD、GSH-Px活性降低,JNK及其磷酸化水平显著增高;而Neu-P11、MLT处理的睡眠限制鼠血糖、胰岛素、MDA、JNK及其磷酸化水平均下降,同时SOD、GSH-Px活性增强。提示Neu-P11、MLT可以改善睡眠限制鼠的抗氧化能力和葡萄糖稳态。结论 Neu-P11通过下调JNK及其磷酸化水平而改善其抗氧化能力,从而改善睡眠限制引起的胰岛素抵抗。

英文摘要：

Aim To investigate the effect of Neu-P11,a novel melatonin receptor agonist,on insulin sensitivity in sleep restricted rats as well as the underlying mechanism. Methods Method of rotating cage was adopted to establish SD rat models of sleep restriction. During the 8 days of sleep restriction,rats were injected intraperitoneally with Neu-P11（20 mg /kg）,MLT（5 mg /kg）,saline respectively every day. Plasma glucose,fasting insulin,malondialdehyde（MDA） levels and enzyme activity of glutathione peroxidase（GSH-Px）,superoxide dismutase（SOD） were detected at the end of experiment,the proteins of JNK and phosphorylated JNK in muscles were measured by Western blot. Results Compared with control group,sleep restricted rats showed increased levels of plasma glucose,fasting insulin,but antioxidative potency decreased. However,in Neu-P11 and melatonin-treated sleep restricted rats,the levels of plasma glucose,fasting insulin and MDA decreased with an increase of SOD,GSH-Px activities. Neu-P11 or melatonin also down-regulated the levels of JNK and phosphorylated JNK which were increased by sleep restriction. These data suggest that glucose homeostasis and antioxidative potency of the chronic sleep restricted rats were protected by Neu-P11 and melatonin. Conclusions Neu-P11 could improve metabolic profiles and insulin resistant induced by sleep restriction,and the regulation of JNK and antioxidative potency may be the underlying mechanism.