糖尿病患者并发抑郁症的几率高，且两者相互作用，互相加重，增加糖尿病患者病死率和致残率。由于缺乏系统的研究方法，糖尿病并发抑郁症的代谢机制至今还不清楚。基于核磁共振1H谱(1H NMR)的代谢组学是研究糖尿病及其并发症整体代谢通路的重要手段，同时可提供代谢途径变化的细节信息。在前期工作中，我们借助该方法发现了与糖尿病及其并发症相关的代谢调控通路变化。本项目拟在我们已有的研究基础上，构建一组稳定、可靠的2型糖尿病并发抑郁症大鼠模型，通过基于1H NMR的代谢组学方法、Western blot技术及病理学方法，研究糖尿病并发抑郁症发生发展过程中前额叶皮层、海马、下丘脑等不同脑区代谢改变，及其与神经可塑性改变、神经元凋亡及胶质细胞增生的关系。预期研究结果有助于阐明2型糖尿病并发抑郁症的代谢机制，也为糖尿病并发症的发病机制和发展演化研究探索新方法，同时也为其它代谢性疾病的病理生理学研究提供新的思路。

Diabetes patients have a high risk of depression. Diabetes and depression will aggravate each other by their interaction, and this will sharply increase the mortality and morbidity of diabetic patients. Due to lacking of systematic research method, metabolic mechanism of diabetes with depression is still not clear. 1H NMR based Metabonomics plays an important role in studying the overall metabolic pathways and providing detail changes in metabolic pathways of diabetes and its complications. During the preliminary work, our study has found some changes in the metabolic pathways of diabetes and its complications through this technique. Based on our previous studies, we will build a set of stable and reliable model of type 2 diabetes rat with depression. We will perform ex vivo NMR-based metabonomics analysis on prefrontal cortex, hippocampus, and hypothalamus from different stages of type 2 diabetic rats with depression. We will perform Western blot, TUNEL and GFAP examinations on these brain tissues to analyze the changes of neuronal plasticity, neurons apoptosis and glial cells proliferation, and to analyze their relationships with metabolic changes. The results of our study can provide a better understanding of the potential metabolic mechanism of diabetes with depression, and will help to explore a new method for the study of the pathogenesis and evolution of diabetes as well as its complications. Our results also will give insights into the study of pathophysiology of other metabolic diseases.