基于星形胶质细胞IR/NDRG2信号研究针刺改善糖尿病认知功能障碍的细胞交流机制

糖尿病患者认知功能下降速度达同龄人2倍之多，痴呆发生风险增高73%。针刺可调理机体代谢紊乱，显著缓解糖尿病症状，我们发现针刺有效改善糖尿病认知功能障碍，但机制尚未阐明。新近发现：星形胶质细胞是脑内胰岛素直接靶细胞，其胰岛素信号参与调节胶质细胞结构与葡萄糖代谢稳态。主要表达于星形胶质细胞的NDRG2参与神经退行性疾病发生发展，抑制肿瘤细胞葡萄糖摄取参与糖代谢，而NDRG2在糖尿病认知功能障碍中的作用尚不清楚。我们前期研究发现，针刺抑制糖尿病小鼠海马星形胶质细胞NDRG2表达，增加突触可塑性，改善糖尿病小鼠学习记忆缺陷，以此推测：针刺通过星形胶质细胞胰岛素信号调节NDRG2，维持突触间隙胶质递质水平，改善海马神经元突触可塑性，减轻糖尿病认知功能障碍。本项目遵循中西医结合理论，系统研究针刺改善认知功能障碍的星形胶质细胞分子信号通路及神经递质细胞交流机制，为治疗糖尿病认知功能障碍提供干预新靶点。

The cognitive decline speed of diabetes mellitus is nearly doubled that of those without it. The risk of incident dementia in diabetes mellitus is increased by 73% higher. Acupuncture can modulate metabolic disturbance and alleviate the symptoms of diabetes. Our pre-experiments found that acupuncture effectively improved cognitive dysfunction in diabetes mellitus, while its mechanism has not yet been elucidated. Most recently, it has been reported that astrocytes are the direct targets cells of insulin in the brain, which involved in regulating the glial structure and the homeostasis of glucose metabolism. NDRG2, which mainly expresses in astrocytes, participates in the development of neurodegenerative diseases and manipulates glucose uptake in tumor cells. Nevertheless, it’s unknown that whether NDRG2 takes part in the cognitive function in diabetes. Our previous study found that acupuncture inhibited NDRG2 expression in hippocampal astrocytes and enhanced synaptic plasticity, leading to ameliorate learning and memory deficits in diabetic mice. Therefore, we propose that acupuncture regulates NDRG2 in astrocytes though insulin signaling, which sustains the level of gliotransmitters in the synaptic cleft, improves synaptic plasticity of hippocampal neurons and relieves cognitive dysfunction of diabetes mellitus. In accordance with the theory of integrated traditional Chinese and Western medicine, this project is aimed to systematically study the mechanisms of acupuncture alleviating diabetic cognitive dysfunction via the astrocytic IR/NDRG2 signaling pathway and intercellular communication by neurotransmitters. This research will provide new targets for therapeutic intervention of cognitive dysfunction in diabetes mellitus.