核因子相关因子2/抗氧化反应元件通路对2型糖尿病大鼠胰岛β细胞功能的影响及其与胰岛素受体底物-2表达的关系

Effects of Nrf2/ARE pathway on islet β cell function and its relationship with the expression of insulin receptor substrate-2 in rats with type 2 diabetes

目的探讨核因子相关因子2(Nrf2)/抗氧化反应元件(ARE)通路对T2DM大鼠胰岛β细胞功能的影响及其与胰岛素受体底物-2(IRS-2)表达的关系。方法雄性Wistar大鼠随机分为正常对照组(NC)、糖尿病模型组(DM)及叔丁基对苯二酚干预组(DM+tBHQ)。连续干预8周,评测胰岛β细胞功能及相关检测。结果 DM+tBHQ组胰岛β细胞功能、总超氧化物歧化酶(T-SOD)浓度、Nrf2、IRS-2蛋白表达及IRS-2磷酸化程度较DM组升高;丙二醛(MDA)、TNF-α浓度较DM组降低(P=0.000)。结论激活Nrf2/ARE通路可通过上调Nrf2下游靶基因在胰岛β细胞中的表达,以减轻氧化应激和慢性炎症反应对IRS-2的进一步损伤,从而延缓胰岛β细胞功能衰退。

Objective To explore the effect of Nrf2/ARE pathway on islet β cell function and its relationship with the expression of insulin receptor substrate-2 （IRS-2） in rats with type 2 diabetes. Methods The male Wistar rats were randomly divided into three groups： normal control group （NC group） ,diabetic model group（DM group）and tertiary-Butylhydroquinone group（DM-＋-tBHQ group）. All the three groups were given continuous intervention for 8 weeks. Islet β cell function was evaluated and other related testing were performed. Results Islet β cell function, total-superoxide dismutase（T-SOD） concentration, the expression of Nrf2 and IRS-2 protein and phosphorylation levels of IRS-2 were higher in DM--tBHQ group than in DM group; Malonaldehyde （MDA） and tumor necrosis factor-α（TNF-α） levels were decreased in DM2＋BHQ group than in DM group（P=0. 000）. Conclusion Activating Nrf2/ARE pathway can ameliorate oxidative stress and chronic inflammation injury on IRS-2, and further delay islet β cell function failure through upregulating the expression of the downstream target genes of Nrf2 in islet β ceils.