荷叶碱对胰岛素抵抗小鼠的干预研究

Intervention study of nuciferine on mice with insulin resistance

目的研究荷叶碱对饮食诱导的胰岛素抵抗小鼠模型的干预作用及其机制。方法以高脂饮食诱导24周的胰岛素抵抗小鼠为模型,分析荷叶碱对肥胖、血糖、胰岛素及稳态模型评估胰岛素抵抗(HOMA-IR)指数的影响,同时探讨其改善胰岛素抵抗的机制。结果经过24周的高脂饮食,模型小鼠形成了明显胰岛素抵抗:肥胖(t=8.1274,P<0.01)、高血糖(P<0.05)、高胰岛素血症及HOMA-IR指数(t=10.215 4,P<0.01;t=7.2897,P<0.01)。荷叶碱有效降低了体重(t=3.750 9,P<0.01)及高糖血症(t=5.236 9,P<0.01)。血清胰岛素水平及HOMA-IR指数也分别降低了60.2%和66.8%(t=6.870 3,P<0.01;t=5.185 6,P<0.01)。荷叶碱通过上调肝组织中IR、IRS1、Glut2及Glut4 m RNA表达改善了糖代谢、提高了胰岛素敏感性(P<0.05),但对IRS2影响不大(t=0.6261,P>0.05)。结论荷叶碱降低了肥胖、高血糖及高胰岛素血症,缓解了胰岛素抵抗,这一作用可能与调控胰岛素信号通路、活化葡萄糖转运信号通路有关。

[Objective]To study the intervention effect and mechanism of nuciferine on mice with insulin resistance model induced by diet. [Methods]The mice with insulin resistance induced by high-fat diet for 24 weeks was as model, the influences of nuciferine on obesity, serum glucose, insulin and homeostasis model assessment of insulin resistence（HOMA-IR） were analyzed, and the mechanism of improving insulin resistance was discussed.[Results]After the high-fat diet for 24 weeks, model mice formed the obvious insulin resistance ： obesity （t =8.127 4, P〈0.01 ）, hyperglycaemia （P〈0.05）, hyperinsulinemia and high HOMA-IR index （t=10.215 4, P〈0.01;t=7.289 7, P〈0.01）. Nuciferine effectively reduced the body weight （t=3.750 9, P〈0.01）and hyperglycemia （t=236 9, P〈0.01）. Serum insulin levels and HOMA-IR index were also decreased by 602% and 668% （t=6. 870 3, P〈0.01; t=5.185 6, P〈0.01 ）. Nuciferine improved the glucose metabolism and insulin sensitivity by up-regulating the expression IR, IRS1, Glut2 and Glut4 mRNA （P〈0.05）, but didn＇t affect IRS2 （t=0.626 1, P〉0.05）.[Conclusion]Nuciferine can inhibit obesity, hyperglycemia and hyperinsulinemia, relieve insulin resistance, which may be related to the regulation of insulin signaling pathway and the activation of glucose transport pathway.