Vof16参与调控Gnb3在糖尿病认知功能障碍中的作用及机制研究

前期我们通过芯片筛选发现lncRNA Vof16是一条高表达于糖尿病认知功能障碍大鼠海马组织中的差异lncRNA，生物信息学的分析提示Gnb3可能为Vof16的调控靶标，且miR-205分别与Vof16、Gnb3有相同的应答元件，进一步体内实验验证Gnb3高表达于糖尿病认知功能障碍大鼠的海马组织。因此，我们分析，糖尿病时Vof16可能通过吸附miR-205，调节Gnb3的表达，进而参与了糖尿病认知功能损害。基于上述研究基础，本课题拟以高糖诱导的海马神经元细胞、糖尿病认知功能障碍大鼠为研究对象，借助体内外实验和分子生物学、形态学等技术和方法，旨在获得Vof16通过吸附miR-205调节Gnb3参与糖尿病认知功能损害的可靠证据，证实Vof16通过吸附miR-205调节Gnb3这一机制在糖尿病认知损害发生、发展中的生物学价值，为糖尿病、认知障碍等相关疾病诊治提供新的靶点和理论基础。

Our previous studies found that a long noncoding RNA Vof16 highly expressed in hippocampus tissue of diabetic rat with cognitive dysfunction by lncRNA microarray. Furthermore, bioinformatic analysis suggested Gnb3 was its candidate target and Vof16 might function as a competing endogenous RNA to “sponge” miR-205 and modulate the concentration and biological function of Gnb3. Gnb3 gene showed highly expressed in hippocampus tissue of diabetic rat with cognitive dysfunction. Thus, we hypothesize that the mechanism of Vof16 “sponge” miR-205 and regulated Gnb3 may affect cognitive damage induced by diabetes. Base on the above research, we choose high glucose induced hippocampal neuron cells and diabetic cognitive dysfunction rats, and aim for the reliable evidence that the mechanism of Vof16 “sponge” miR-205 and regulated Gnb3 is involved in cognitive damage induced by diabetes by the technologies of molecular biological and morphological methods, and in vitro & in vivo. We hope to investigate the biological values and the molecular mechanisms of the mechanism of Vof16 “sponge” miR-205 and regulated Gnb3 in the development of diabetic cognitive dysfunction in more details. Moreover, the current project will provide new targets and theoretical basis for the diagnosis and treatment of diseases such as diabetes and cognitive dysfunction.