关键词: Ⅱ型糖尿病(T2D), 阿尔兹海默症(AD), 胰岛素抵抗, 老年斑, 水迷宫实验, 小鼠

Abstract: Objective To construct a mouse model of type 2 diabetes mellitus (T2D) combined with Alzheimer's disease (AD).Methods The male (APP/PS1^+/+/db/db^+/+) mice and female (APP/PS1^-/-/db/db^+/-) mice were hybridized.The male and female offspring with genotype (APP/PS1^+/-/db/db^+/-) were mated,and produced the offspring with genotype (APP/PS1^+/+/db/db^-/-) as the model group (group M);with genotype (APP/PS1^-/-/db/db^+/+) and (APP/PS1^-/-/db/db^+/-) as the control group (group C).Thirty mice randomly selected from 2 groups were divided into 3 subgroups with the age of 4,14 and 25 weeks old respectively.The metabolic indexes,such as body weight,fasting blood glucose,postprandial blood glucose,blood sugar insulin content and insulin resistance index,of mice in different groups were detected.The learning and memory ability of mice were detected through the water maze test.The anatomical feature of brain tissue (brain weight and cortical and hippocampal area) were detected via cresyl violet staining,and the microglia,astrocytes,and the content and distribution of A protein and senile plaques (SP) in cortex and hippocampus were detected by immunohistochemistry staining.Results Animals in M group,starting from 4 weeks of age,body weight index was significantly increased compared with C group on blood glucose,insulin content and insulin resistance (P<0.01).While the brain weight,search platform latency,the original platform quadrant time ratio were significantly decreased (P<0.01).At 14 weeks of age,area of cerebral cortex and hippocampus decreased significantly (P<0.01),tau protein phosphorylation level was significantly increased (P<0.01).At 25 weeks of age,cortex and hippocampus A beta deposition,and the formation of SP at the same time,microglia and astrocytes increased significantly (P<0.01).Conclusion The established mouse model of T2D combined with AD,which provided a platform for study of the relationship between the two diseases and development of therapeutic drugs.

Key words: Type 2 diabetes mellitus (T2D), Alzheimer's disease (AD), Insulin resistance, Senile plaque (SP), Water maze test