橙皮苷改善肥胖小鼠糖脂代谢的机制研究

Protection mechanisms of hesperidin on mouse with insulin resistance

该研究阐明橙皮苷对高脂饮食诱导的肥胖小鼠糖脂代谢紊乱的干预机制。40只雄性C57小鼠,根据饮食随机分为对照组、肥胖组、橙皮苷低剂量组及高剂量组,每组各10只。喂养16周后检测各组小鼠体重、肝指数、内脏脂肪指数,评价糖代谢状况(葡萄糖糖耐量、血糖、胰岛素水平及HOMA-IR)及血脂情况;Real-time PCR法检测肝脏胰岛素信号通路(IR,IRS1,Glut2,Glut4)、脂代谢途径(SREBP-1c,FAS,ACC,PPARα)关键基因及AMPK表达水平。经过16周喂养,肥胖组小鼠明显肥胖,体脂沉积显著(P<0.01),葡萄糖耐量降低(P<0.05)。血糖、血脂、胰岛素水平及HOMA-IR指数均高于对照组(P<0.05)。橙皮苷干预后,无论低剂量组还是高剂量组小鼠体重、血糖、血脂均较肥胖组明显降低(P<0.05),血清胰岛素水平及HOMA-IR亦显著下降(P<0.05)。其中大剂量组获益明显(P<0.05)。橙皮苷能够上调AMPK mRNA(P<0.05),继而影响胰岛素信号通路中IR,IRS1,Glut2/4的mRNA表达(P<0.05),同时降低脂代谢相关基因(SREBP-1c,FAS,ACC)的表达(P<0.05),并升高PPARαmRNA水平(P<0.05)。大剂量组变化尤为明显(P<0.05)。橙皮苷降低了肥胖、高血糖、高血脂,缓解了胰岛素抵抗,这一作用可能与其活化AMPK继而调控胰岛素信号通路及脂质代谢信号通路等密切相关。

To explore the effects of hesperidin on glycolipid metabolic disorders and its mechanism in mice induced by high-fat diet, 40 male C57 mice were randomly divided into control group, OB group, low dose group （OB ＋ hes-low） and high dose group （OB ＋ hes-high） according to the diet. After 16 weeks, the body weight, liver index and visceral fat index in all mice were detected. The glu- cose metabolism indications （blood glucose, insulin levels and HOMA-IR） and serum lipid levels were evaluated. The mRNA expres- sion of insulin signaling pathway genes（IR, IRS1, Glut2, Glut4）, lipid metabolism pathway genes（SREBP-lc, FAS, ACC, PPARα） and AMPK were analyzed by Real-time PCR. After 16-week feeding, the indicators in OB group were higher than those in control group, including body weight, body fat deposition, serum glucose, serum lipid, serum insulin and HOMA-IR index （P 〈 0. 05 ）. And impaired glucose tolerance occurred in the OB group （P 〈 0. 05）. Treating with hesperidin, whether in low or high dose, attenuated these changes （P 〈 0. 05 ）, especially in high dose group （P 〈 0. 05 ）. Hesperidin, especially in high dose, upregulated the mRNA ex- pressions of AMPK （P 〈0. 05）, which had impact on the gene expressions of insulin signaling pathway （IR, IRS-1, Glut2/4） （P 〈 0. 05 ） and lipid metabolism related genes （ SREBP-1 c and Fas and ACC） （P 〈 0. 05 ）. The activatory effect of hesperidin on the mR- NA expressions of PPARα was also observed （P 〈 0. 05）, especially in high dose group （P 〈 0. 05）. Hesperidin inhibits obesity, hy- perglycemia, hyperlipemia and attenuates insulin resistance. These effects might be closed related to the activation of AMPK, which regulate the insulin signaling pathway and lipid metabolism.