miR-1249在野菊花水提物改善妊娠期糖尿病胰岛β细胞氧化损伤中的功能和机制研究

High oxidative stress state of GDM could induce pancreatic β cell-based islet function injury. Preliminary study has found that flos chrysanthemi indici aqueous extract has the function of protecting pancreatic β cell as the antioxidant, and the effect of lowering blood glucose in GDM rats, however, the mechanism is still unclear. Chip inspection has found that miR-1249 is differentially expressed in pancreatic β cells of GDM rats before and after the intervention of flos chrysanthemi indici aqueous extract. Preliminary experiment has detected that silent miR-1249 could improve oxidative damage and inhibit apoptosis of pancreatic β cells; software has predicted NFE2L2 to be the target gene; flos chrysanthemi indici aqueous extract could down-regulate miR-1249 expression and up-regulate NFE2L2 expression. Besides, flos chrysanthemi indici aqueous extract could possibly prevent GDM genesis and development through miR-1249/NFE2L2 mechanism. Our research attempted to demonstrate the effect of miR-1249 in oxidative damage of pancreatic β cells from positive and negative aspect; reveal its molecular mechanism based on the clue of NFE2L; systematically evaluate function and mechanism of flos chrysanthemi indici aqueous extract in improving oxidative damage of GDM pancreatic β cells. The research has revealed unknown function and mechanism of miR-1249 from the angle of view that natural antioxidant could prevent GDM. The research thought of this project has not been reported yet, so it has certain original innovativeness.

妊娠期糖尿病（GDM）的高氧化应激状态可诱发胰岛β细胞功能损伤。前期发现，野菊花水提物具有抗氧化、保护胰岛β细胞功能、降低GDM鼠血糖的作用，但机制未明。芯片检测发现 miR-1249在野菊花水提物干预前后GDM鼠胰岛β细胞中差异表达。预实验表明，沉默miR-1249可改善胰岛β细胞的氧化损伤、抑制其凋亡；软件预测NFE2L2为其靶基因；野菊花水提物可下调miR-1249表达、上调NFE2L2表达。提示野菊花水提物可能通过miR-1249/NFE2L2机制预防GDM发生发展。本研究拟正反论证miR-1249在胰岛β细胞氧化损伤中的作用；以NFE2L2为线索揭示其分子机制；系统评估野菊花水提物改善GDM胰岛β细胞氧化损伤的功能与机制。从天然抗氧化物防治GDM的视角揭示miR-1249的未知功能与机制，为GDM机制研究补充依据，也为其医学营养治疗提供新线索。研究思路未见类似报道，具源头创新性。

妊娠期糖尿病（GDM）的高氧化应激状态可诱发胰岛β细胞功能损伤。前期发现，野菊花水提物具有抗氧化、保护胰岛β细胞功能、降低GDM鼠血糖的作用，但机制未明。芯片检测发现 miR-1249在野菊花水提物干预前后GDM鼠胰岛β细胞中差异表达。预实验表明，沉默miR-1249可改善胰岛β细胞的氧化损伤、抑制其凋亡；软件预测NFE2L2为其靶基因；野菊花水提物可下调miR-1249表达、上调NFE2L2表达。提示野菊花水提物可能通过miR-1249/NFE2L2机制预防GDM发生发展。本研究通过正反论证miR-1249在胰岛β细胞氧化损伤中的作用；以NFE2L2为线索揭示其分子机制；系统评估了野菊花水提物改善GDM胰岛β细胞氧化损伤的功能与机制。 研究结果发现：GDM 孕妇较正常孕妇，血清中的miR-1249含量增高9.2倍；miR-1249显著增加了小鼠胰岛组织中氧化应激标志物（MDA）含量、胰岛体积严重缩小，细胞排列松散、抗氧化酶CAT、 SOD和 GSH-PX活性明显下降，NFE2L2及PDX-1、Insulin表达明显下调，而野菊花水提物干预可逆转miR-1249 过表达对小鼠胰腺组织氧化损伤的影响。本研究从天然抗氧化物防治GDM的视角揭示miR-1249的未知功能与机制，为GDM机制研究补充了依据，也为其医学营养治疗提供新线索。