Nrf2激动剂通过激活自噬保护胰岛β细胞氧化应激损伤的作用及机制

The function of pancreatic islet β cell is a key target for prevention and cure of diabetes mellitus. The study have confirmed that Nrf2 can protect oxidative stress damage of islet , our preliminary study shows, the expression of Nrf2 was up-regulated in newly-onset diabetes of human and mouse islets. Along with the gradually development of diabetes , Nrf2 system gradually decompensates, β cell function is decreased accordingly, so new ways to strengthen the activity of Nrf2 is important.The activation of autophagy is an important protective mechanism for oxidative stress damage. Our previous results showed, Nrf2 can promote autophagic activity, and decrease the expression of ubiquitin poison. Therefore, we speculate that in pancreatic beta cells, Nrf2 agonist, in addition to the direct induction of cell protective phase II detoxification enzymes and antioxidant protein, also can promote autophagy strengthen clear protect islet function of beta cell toxicity of ubiquitinated proteins.

胰岛β细胞功能保护是糖尿病防治的关键靶点。研究证实Nrf2能够保护胰岛β细胞的氧化应激损伤，我们前期研究显示，新发糖尿病患者和小鼠胰岛的Nrf2表达是上调的。随着糖尿病的发展及体内氧化应激状态的逐渐加剧，Nrf2系统逐渐失代偿，β细胞的功能进行性下降，因此，寻找途径加强Nrf2活性及寻找Nrf2的其他作用方式非常重要。激活自噬是细胞抗氧化应激损伤的重要保护机制。我们的前期研究结果显示，nrf2能够促进自噬活性，同时降低泛素化毒物的表达。因此，我们推测在胰岛β细胞中，Nrf2激动剂，除直接的诱导细胞保护性的II相解毒酶及抗氧化蛋白外，还可促进自噬加强对β细胞毒性泛素化蛋白的清除保护胰岛功能。