PGC1α的抗氧化应激效应在锌α 2糖蛋白增加胰岛素敏感性中的作用及其机制

胰岛素抵抗是2型糖尿病发病的主要原因，氧化应激可直接导致胰岛素抵抗。抑制氧化应激可有效地改善胰岛素抵抗而防治2型糖尿病。新的脂肪细胞因子锌α2糖蛋白（ZAG）具有减重和改善胰岛素抵抗的作用，但具体机制尚不清楚。我们前期的实验提示,ZAG能促进脂肪组织中抗氧化应激因子过氧化物酶增殖物激活受体共激活因子（PGC1α）。因此本课题从人整体水平和细胞水平探讨ZAG与氧化应激的关系，观察ZAG对PGC1α的影响以及涉及的细胞内信号通路，预期将阐明ZAG通过促进PGC1α的表达，抑制ROS产生，增加胰岛素敏感性的抗氧化应激机制，为开发针对ZAG的药物提供实验依据。

Insulin resistance is the main cause in the pathogenesis of type 2 diabetes. Oxidative stress can directly lead to insulin resistance. Inhibition of oxidative stress can effectively improve the insulin resistance and prevention of type 2 diabetes. New adipocytokine zinc α2 glycoprotein (ZAG) can decrease body weight and improve insulin resistance, but the detailed mechanism is unclear. Our previous studies demonstrated that ZAG promoted the expression of anti-oxidative stress factors peroxidase enzyme proliferator-activated receptor co-activator factor 1α (PGC1α) in adipose tissue of mice. In the present study, we will explore the relationship between ZAG and oxidative stress, the effect of ZAG on PGC1α and the possible intracellular signaling pathways by using gene over-expression and RNA interference technology. The expected results will shed light on ZAG improves insulin sensitivity via against oxidative stress by increasing the expression of PGC1α, inhibiting ROS production. It will provide the experimental basis for the development of ZAG as anti-oxidant drugs.