糖尿病并发抑郁症（DD）发病隐匿、易反复且致死率高。海马突触可塑性损伤与DD发生密切相关，但机制未明。课题组前期发现，DD大鼠海马炎症环境可诱发小胶质细胞（MG）、星形胶质细胞（As）呈激抑失衡状态，谷氨酸受体（NR）被过度激活。最新研究表明，“Quad-Partite”突触将MG、As、突触前膜和后膜构成一个结构整体单元可系统阐明突触损伤的特点与规律，而NR是其可塑性的阀门分子。因此，本课题拟综合运用膜片钳、LSC、HCS、FCM等现代技术，从整体-细胞两方面、形态-功能-分子三水平，探明“糖尿病时，海马‘Quad-Partite’突触MG-As激抑失衡触发炎症级联反应，导致KYN和FKN双信号通路异常，共同介导NR过激致海马突触可塑性损伤，进而并发DD”的分子机制，并采用“滋阴益气、化瘀解郁”立法方药干预反证DD“虚、瘀、郁”的中医病机，可为其发病机制和有效防治提供新思路。

Diabetes mellitus with depression (DD) is an insidious, relapsing and highly lethal disease. Previous studies showed hippocampal synaptic plasticity damage was closely related to the occurrence of DD, but its mechanism is not clear yet. Previous studies have found the inflammatory environment in the hippocampus of DD rats could reduce the structure and function of the hippocampal microglia (Mg) and astrocytes (As) were changed, showing an imbalance state of agitation and inhibition, and glutamate receptor(NR) was overactivated. The latast researches show that the "Quad-Partite" synapse combines MG, As, presynapticelement and postsynapticelement into one structural unit to systematically elucidate the characteristics and regularity of synaptic injury, while NR is the valve molecule of synaptic plasticity. Consequently, the subject intends to further investigate the molecular mechanism of DD which associated with the imbalance of Mg-As stimulation in hippocampal "Quad-Partite" synapse in diabetic state triggers inflammatory cascade reactions, resulting in the abnormal KYN and FKN dual signal pathways, which together mediate NR over-stimulation and cause damages of hippocampal synaptic plasticity, and further complicates DD, on the whole - cell aspect and morphology - function - molecular level by the modern technologies of patch clamp, LSC, HCS and FCM etc.. The theory of “enriching yin and nourishing qi, disperse blood stasis and resolve depression” was applied to disproof the pathology (asthenia, stasis and depression) of DD, which could provide a novel ideas for the research of its pathogenesis and prevention.