基于Keap1-Nrf2/ARE信号通路研究牛磺酸对胰岛素抵抗模型大鼠氧化应激的影响

Effects of Taurine on Oxidative Stress in Rats with Insulin Resistance Based on Keap1-Nrf2/ARE Signaling Pathway

关键词:  牛磺酸  2型糖尿病  氧化应激  Keap1-Nrf2/ARE

Key words:  taurine  type 2 diabetes  oxidative stress  Keap1-Nrf2/ARE

摘要:

目的 通过研究牛磺酸对胰岛素抵抗大鼠模型的血糖、血脂、氧化应激指标以及Keap1-Nrf2/ARE信号通路重要靶点的影响，并探讨其分子调控机制。方法 建立胰岛素抵抗SD大鼠模型，测定连续灌胃给药7周后正常组、模型组、二甲双胍组、牛磺酸高剂量组以及牛磺酸低剂量组的空腹血糖（fasting blood glucose，FBG）、空腹胰岛素、甘油三酯（triglyceride，TG）、总胆固醇（total cholesterol，TC）、高密度脂蛋白、低密度脂蛋白，计算胰岛素抵抗指数；采用酶联免疫吸附试验法测定肝组织中超氧化物歧化酶（superoxide dismutase，SOD）、丙二醛（malondialdehyde，MDA），运用RT-PCR技术检测肝组织中Nrf2、Keap1、HO-1、NQO1 mRNA的表达量。结果 给药7周后，与模型组比，牛磺酸高剂量组胰岛素抵抗大鼠FBG、空腹胰岛素降低（P<0.05），血清TC、TG水平也降低（P<0.05）；大鼠肝组织的SOD升高、MDA降低（P<0.05）；肝组织中HO-1、NQO1、Nrf2的mRNA水平上调（P<0.05）， Keap1 mRNA水平下调（P<0.01）。结论 牛磺酸可调节糖尿病大鼠的血糖、血脂，改善模型大鼠氧化应激状态，减轻胰岛素抵抗，可能与其调控Keap1-Nrf2/ARE信号通路中关键基因表达从而改善氧化应激有关。

Abstract:

OBJECTIVE To study the effects of taurine on blood glucose, lipids, oxidative stress indicators and important targets of Keap1-Nrf2/ARE signaling pathway in insulin-resistant rat models, and to explore its molecular regulatory mechanism. METHODS SD rat model of insulin resistance was established, and fasting blood glucose(FBG), fasting insulin, triglyceride (TG), total cholesterol(TC), high density lipoprotein, low density lipoprotein in normal group, model group, metformin group, taurine high-dose group and taurine low-dose group was determined after continuous intragastric administration for 7 weeks, insulin resistance index was calculated. ELISA method was used to measure superoxide dismutase(SOD), malondialdehyde(MDA) in liver tissue, and RT-PCR was used to detect Nrf2, Keap1, HO-1, NQO1 mRNA expression level. RESULTS After 7 weeks of administration, compared with the model group, FBG and fasting insulin of insulin resistant rats in taurine high-dose group were decreased(P<0.05), and the levels of TC and TG were decreased(P<0.05); SOD in liver tissue of rats was increased, MDA was decreased(P<0.05); the mRNA levels of HO-1, NQO1 and Nrf2 in liver tissues were up-regulated(P<0.05) and Keap1 mRNA was down-regulated(P<0.01). CONCLUSION Taurine can regulate blood glucose and lipids in diabetic rats, improve oxidative stress and reduce insulin resistance in model rats. It may be related to the regulation of key gene expression in Keap1-Nrf2/ARE signaling pathway to improve oxidative stress.