miR-320c参与调控1型糖尿病早期胰岛β细胞凋亡的作用及机制研究

凋亡是1型糖尿病（T1DM）早期胰岛β细胞死亡的主要方式。深入研究T1DM早期β细胞凋亡调控机制有助于更好的保护β细胞。我们的前期试验已证实血清miR-320c在新诊断T1DM患者中与健康人群具有显著差异性；生物信息学分析及既往研究提示miR-320c预测靶基因参与细胞凋亡相关信号通路；利用链脲佐菌素处理大鼠胰岛素瘤细胞系（INS-1细胞）造成细胞凋亡，发现miR-320c在细胞及上清中含量均有所增加；并且在NOD动物模型中血清miR-320c表达水平在胰岛炎期即已发生改变。因此，我们推测miR-320c参与调控T1DM早期胰岛β细胞凋亡。本项目拟在前期研究基础上，构建T1DM动物模型（NOD鼠）及发病早期（胰岛炎期）细胞模型，从动物整体水平及组织细胞水平多方面探讨miR-320c参与调控T1DM早期β细胞凋亡的作用、分子机制及上下游信号网络，为T1DM的防治提供新的思路和靶点。

Apoptosis is the main pattern for the death of beta cells in early type 1 diabetes mellitus (T1DM). Researches on the regulatory mechanism of early onset of beta-cell apoptosis in T1DM are benefit to protect the beta-cell function. Our pilot study have been confirmed the significant differential of serum miR-320c between new-onset patients with T1DM and healthy controls. Bioinformatics analysis and previous studies have implied the target genes of miR-320c were involved in the pathway of apoptosis. MiR-320c were both increased in the medium and cells in STZ-treated INS-1 cells. Serum miR-320c was increased in insulitis phase prior to glucose elevation in prediabetic NOD mice. We therefore hypothesized that miR-320c could regulate the beta-cell apoptosis in early T1DM. This project aimed to further explore the role and molecular mechanism of miR-320c on the regulation of beta-cell apoptosis in early T1DM through animal models (NOD mice) and cell models (cytokines-treated beta cells), providing a new way and target for the prevention and control of T1DM.