基于micro PET/CT 研究补肾活血法改善糖尿病脑病小鼠葡萄糖代谢的作用及其相关机制

Diabetic encephalopathy is the cognitive impairment and changes of the brain's physiology and structure caused by diabetes mellitus. Its early diagnosis and treatment is of great social significance. In Traditional Chinese Medicine, it is regarded that kidney deficiency and blood stasis is the main pathogenesis of diabetic encephalopathy. So tonifying kidney and promoting blood circulation is the principle of Chinese medicine. Our previous studies have confirmed that “Bushen Huoxue Decoction”, which is composed of modified Wuzi Yanzong prescription and leech, can significantly improve the cognitive function of patients with type 2 diabetes mellitus. 18 F-FDG PET/CT can detect the functional changes in the brain before the structure changes, therefore, it can be used to diagnose early diabetic encephalopathy. Insulin like growth factor system and PI3K/Akt signal transduction pathway are key factors and pathway in regulating glucose metabolism in the brain. The regulation of these factors and pathway can prevent and treat diabetic encephalopathy. In this study, the Kkay mice are chosen as the animal model of diabetic encephalopathy. Y maze and Morris water maze will be utilized to detect the cognitive function improvement efficacy in the mice with diabetic encephalopathy. The glucose metabolism in the brain will be the point of penetration. The image changes of 18F-FDG PET/CT will be applied to observe the improving effect of "Bushen Huoxue Decoction" on the brain glucose metabolism in the mice with diabetic encephalopathy. Molecular biology method will be employed to explore the effects on IGF system and PI3K Akt signal transduction pathway, which is closely related to the glucose metabolism in the brain. Our study aims at elaborating the possible underlying mechanism of traditional Chinese medicine in the prevention and treatment of diabetic encephalopathy.

糖尿病脑病是指糖尿病引起的认知障碍和大脑的神经生理及结构改变。中医认为“肾虚血瘀”是糖尿病脑病的主要病机，补肾活血为其中医治法。前期研究证实“补肾活血方”可有效改善2型糖尿病患者的认知功能。补肾活血方是由加味五子衍宗方加水蛭组成的。18 氟-脱氧葡萄糖PET/CT可以在糖尿病脑病出现结构改变之前，发现其功能性改变，早期诊断糖尿病脑病。胰岛素样生长因子系统和PI3K/Akt信号转导通路是调节脑葡萄糖代谢的关键级联通路。本研究拟以Kkay小鼠为糖尿病脑病动物模型，应用Y迷宫及Morris水迷宫检测其对糖尿病脑病小鼠认知功能的改善作用，以大脑葡萄糖代谢为切入点，从PET/CT图像改变观察“补肾活血方”对糖尿病脑病小鼠葡萄糖代谢水平的改善作用，采用分子生物学方法研究其对与葡萄糖代谢密切相关的IGF系统及PI3K-Akt 信号转导通路的影响，阐述中医补肾活血法预防及治疗糖尿病脑病的相关机制。