海马铁沉积在T2DM认知功能损害中的作用机制及磁共振评估研究

2型糖尿病（T2DM）易导致以学习记忆损害为主的认知功能损害，但其机制尚未明确。研究发现T2DM患者存在机体铁代谢失衡，可能是T2DM的复杂不利因素影响了以铁调素为核心的铁代谢过程。过量的铁如果在大脑沉积可通过氧化应激损伤脑细胞导致认知功能损害，影像学研究发现海马是T2DM患者出现功能异常的关键脑区，因此本研究假设海马铁沉积是T2DM认知功能损害的重要原因。本研究拟采用磁共振定量磁化率成像（QSM）技术定量分析海马的铁沉积水平，探讨海马铁沉积与T2DM认知功能损害之间的关系；检测T2DM背景下大鼠海马的铁代谢相关蛋白异常及氧化应激损伤；对T2DM大鼠脑铁调素表达进行干预，寻找T2DM认知功能损害的干预靶点；同时验证QSM在T2DM海马铁沉积检测中的准确性与评估价值。本研究可从海马铁沉积角度揭示T2DM认知功能损害的机制，并为疾病的诊断、治疗和监测提供新的依据。

Type 2 diabetes mellitus (T2DM) leads to cognitive impairment in the subdomains of learning and memory. However, its mechanism remains unknown. It has been reported that T2DM patients exhibit metabolic disorders of iron. Various factors existing in T2DM affect the iron metabolism which is regulated by hepcidin. Iron deposition in central nervous system result in cognitive impairment via neural oxidative stress injury. Neuroimaging studies demonstrated that hippocampus is the key dysfunction area in T2DM patients. Therefore, we assume that T2DM cognitive impairment is closely associated with the hippocampal iron deposition. The present research intends, first, to determine the hippocampal iron deposition with quantitative susceptibility mapping (QSM) and investigate its relationship with T2DM cognitive impairment; second, to investigate the abnormity of proteins involved in iron metabolism and oxidative stress injury in hippocampus; third, to intervene the hepcidin expression in T2DM rats brain which may help in seeking for the approach to prevent the cognitive impairment; finally, to verify the accuracy and evaluative meaning of QSM in T2DM hippocampal iron deposition. The current research can reveal the mechanisms of cognitive impairment in T2DM from the perspective of hippocampal iron deposition, and lay a foundation for diagnosis, treatment and monitoring for T2DM-associated cognitive impairment.