糖尿病并发抑郁症（DD）是严重威胁人类健康的疾病,迄今机制不清。课题组在多项国家自然科学基金项目的支持下发现：DD发生与小胶质细胞（MG）活化及其诱导的海马神经血管单元（NVU）联动损伤密切相关。因此，阐明MG的活化机制是理清DD发病机制，开展DD防治的关键环节。Tim-3是MG活化的标志，也是调节MG M1/M2型活化状态转变的核心分子。本项目拟采用高内涵、流式细胞术、悬液芯片等技术，结合Tim-3抑制剂、激动剂等，从在体、离体两方面，揭示“DD状况下高水平皮质醇(COR)通过GR/TLR4扣动Tim-3、启动海马MG持续活化”的分子机制；并采用“滋阴益气、化瘀解郁”立法方药干预，反证“虚、瘀、郁”中医病机，丰富其科学内涵。以Tim-3为靶点的海马MG活化机制研究将为中药防治DD提供新的思路与靶点。

Diabetes mellitus with depression (DD) is a serious threat to human health, but the pathogenesis is not clear by now. Under the support of a number of National Natural Science Foundation, we found that DD was closely related to the activation of hippocampal microglia (MG) and the damage of neurovascular unit (NVU) it caused. Therefore, to clarify the mechanism of MG activation is the key link of the DD’s pathogenesis. Tim-3 is not only an activation marker of MG , but also an important protein regulating MG M1/M2 activation state. The project aims to use HCS, FCM, Luminex technology and Tim-3 inhibitor, activator, revealing the activation of MG mediated by Tim-3 in hippocampus in DD. The theory of “enriching yin and nourishing qi, disperse blood stasis and resolve depression” was applied to disproof the pathology (asthenia,stasis, depression) of DD, which provide a new idea for the research of its pathogenesis and a new target for the prevention.