白杨素对胰岛素抵抗小鼠的干预研究

目的:研究白杨素对胰岛素抵抗小鼠模型的干预作用及其相应机制。方法:40只雄性C57小鼠,根据饮食随机分为对照组、胰岛素抵抗组、白杨素低剂量组及高剂量组,每组各10只。喂养24周后检测各组小鼠体重、肝指数和脂肪指数,评价胰岛素抵抗状况(血糖、胰岛素水平及HOMA-IR)及氧化应激水平(SOD、GSH-Px和MDA);real-time PCR检测肝脏胰岛素信号通路分子(IR、IRS1、IRS2、Glut2和Glut4)及炎症分子(TNF-α、IL-1β、IL-6和NF-κB)mRNA表达水平。Western blot检测肝脏关键信号蛋白(IRS1和p65)及其磷酸化的水平。结果:经过24周干预后,胰岛素抵抗组小鼠明显肥胖,体脂沉积显著(P0.01),血糖、胰岛素水平及HOMA-IR指数均高于对照组(P0.01),且肝脏氧化应激增加(P0.05),成功建立胰岛素抵抗模型。白杨素干预后,无论低剂量组还是高剂量组小鼠体重、血糖较胰岛素抵抗组上升缓慢(P0.05),血清胰岛素水平及HOMA-IR亦明显降低(P0.05),肝脏氧化应激水平明显下降(P0.05)。白杨素能够上调胰岛素信号通路中IR、IRS1、IRS2、Glut2及Glut4的mRNA表达,同时降低各炎症因子的表达,对NF-κB有抑制作用(P0.05)。其中高剂量组在炎症抑制方面更强(P0.05)。Western blot实验结果提示白杨素的改善作用与上调p-IRS1及下调p-p65相关。结论:白杨素降低了肥胖、高血糖及高胰岛素血症,缓解了胰岛素抵抗及氧化应激,这一作用可能与其调控胰岛素信号通路及抑制炎症因子表达密切相关。

Protective effect of chrysin on mice with insulin resistance

AIM: To explore the effects of chrysin on insulin resistance (IRe) in a mouse model. METHODS: Male C57 mice were randomly divided into control group, IRe group, low-dose chrysin group (IRe+chrysin-low) and high-dose chrysin group (IRe+chrysin-high). After 24 weeks, the body weight, liver index and fat mass in all mice were detected. The blood glucose, insulin level and HOMA-IR were measured to determine the changes of the insulin resistance in the animals. The oxidative stress (SOD, GSH-Px and MDA) was also measured. The mRNA expression of insulin signaling pathway molecules (IR, IRS1, IRS2, Glut2 and Glut4) and inflammatory factors (TNF-α, IL-1β, IL-6 and NF-κB) was analyzed by real-time PCR. The protein levels of IRS1 and p65, and their phosphorylation were detected by Western blot. RESULTS: After 24-week intervention, the indicators in IRe group were higher than those in control group, including body fat deposition, serum glucose, serum insulin, HOMA-IR and liver oxidative stress (P<0.01), indicating that the model of insulin resistance was successfully established. Low dose and high dose of chrysin decreased the body weight, serum glucose, serum insulin and HOMA-IR in the IRe mice (P<0.05). The liver oxidative stress was also reduced in both groups (P<0.05). However, no statistical difference of the indexes between IRe+chrysin-low group and IRe+chrysin-high group was observed. Chrysin upregulated the mRNA expression of IR, IRS1, IRS2, Glut2 and Glut4 (P<0.05), and down-regulated the mRNA expression of various inflammatory factors. The inhibitory effect of chrysin on the mRNA expression of NF-κB was observed (P<0.05), especially in high dose group (P<0.05). It was confirmed that the effect of chrysin on liver IRe was related with the increase in the p-IRS1 levels and decrease in the p-p65 levels by Western blot. CONCLUSION: Chrysin inhibits obesity, hyperglycemia and hyperinsulinemia, and relieves insulin resistance and oxidative stress, which might be closely related to the regulation of insulin signaling pathway and the inhibition of inflammatory factor expression.