Abstract: Objective To investigate the effect of Analog of APP 5-mer peptide P165 on learning and memory abilities in rats with type 2 diabetes mellitus(T2 DM). Methods A total of 34 male Sprague Dawley(SD) rats were randomly divided into 4 groups: control group(C), diabetes mellitus group(DM), DM with low dose P165 group(DM+ low dose P165), DM with large dose P165 group(DM+ large dose P165). DM models were induced by high-fat and sugar diet and intraperitoneal injection of STZ(35 mg/kg). The P165 was fed through a gastric tube every day; whereas the C and DM groups were given 0.9% normal saline. Eight weeks after administration, Morris water maze was used to perform training trial and probe trial in order to detect spatial learning and memory abilities. The body weight and serum glucose were measured every week. Results After 8 weeks, the escape latency increased significantly in the DM group(P<0.01) than in the group C; in the DM+ low dose P165 and DM+ large dose P165 groups, it decreased significantly than in the DM group(P<0.05). In the Spatial probe experiment, the first time passing hidden platform prolonged significantly(P<0.05) and the distance of swimming in the quadrant of hidden platform decreased significantly in the DM group than in group C(P<0.01). But the first time passing hidden platform decreased significantly in the DM+ low dose P165 and DM+ large dose P165 than in the DM group. The serum glucose level showed no significant difference in the 3 T2 DM groups in the period of experiment. Conclusion The learning and memory abilities have been impaired in T2 DM rats. The escape latency and the first time passing hidden platform can be prolonged significantly in T2 DM rats. P165 can ameliorate the learning and memory abilities in T2 DM rats but not influence the serum glucose level.

Key words: analog of APP 5-mer peptide P165, type 2 diabetes, morris water maze, learning and memory, model, rat