2型糖尿病认知障碍发生机制研究进展

2型糖尿病是诱发认知障碍的独立危险因素之一，其发病机制除与长期高血糖引起的糖毒性、胆固醇代谢异常密切相关外，还与中枢胰岛素信号转导异常、下丘脑-垂体-肾上腺轴（hypothalamic-pituitary-adrenal axis, HPA）功能亢进有关，而多种生化指标及细胞信号通路的异常不仅增加β淀粉样蛋白引起的神经毒性作用，诱发神经细胞凋亡，而且可加剧脑微血管病变，破坏血脑屏障的正常生理结构及功能，促进2型糖尿病认知障碍的发生发展。本文就2型糖尿病认知障碍进程中的上述关键因子展开讨论，探讨相关防治策略，为开发2型糖尿病认知障碍的治疗药物奠定基础。

Research Advances on Mechanism of Cognitive Impairment in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus is one of the independent risk factors that can induce cognitive impairment. Except for chronic hyperglycemia-induced glucotoxicity and disorder of cholesterol metabolism, impaired insulin signaling, hyperfunction of HPA axis (hypothalamic-pituitary-adrenal axis) and other factors are also attributed to the pathogenesis of diabetic cognitive dysfunction. Furthermore, many biochemical indicators and abnormal cell signaling pathways not only increase the neurotoxicity of amyloid-β peptide and induce nerve cells apoptosis, but also aggravate cerebral microvessels disease and damage both the structure and function of blood-brain barrier and then promote the occurrence and development of cognitive impairment in type 2 diabetes mellitus. This paper reviewed the key mechanisms in the process of cognitive impairment in type 2 diabetes mellitus and presented the strategies for its prevention and treatment, and subsequently laid the foundation for development of drugs which can effectively treat diabetic cognitive dysfunction.