Abstract: Objective To investigate the effect of analog P165 of APP5-mer peptide and rosiglitazone on change of spatial reference learning and memory ability in type 3 diabetes mellitus rats. Methods Healthy adult male rats of Sprague Dawley(SD) strain were randomly divided into 4 groups: Control group, type 3 diabetes mellitus(T3DM) group, T3DM P165 treatment group, and T3DM rosiglitazone treatment group. T3DM models were induced by intracerebroventricular injection of Streptozotocin(STZ, 3 mg/kg) bilaterally. P165 groups were treated with gastric P165(355 μg/kg) and rosiglitazone group was treated with gastric rosiglitazone(2 mg/kg) for 4 weeks, whereas the model group and control group were given 0.9% normal saline. Then,learning and memory ability was detected by Morris water maze test. Body weight and serum glucose level were recorded. The rat serum insulin, glucagon, insulinlike growth factor-1(IFG-1) was detected by ELISA method. Results In the Morris water maze test, compared with control group, the escape latency increased significantly(P<0.01) in model group. Compared with model group, the escape latency decreased significantly(P<0.05) in the groups treated with P165 and rosiglitazone. The serum IGF-1 level decreased significantly in the model group(P<0.05) than the control group. The serum IGF-1 level increased significantly in P165 treated group(P<0.01). The body weight and the serum glucose, insulin, and glucagon had no significant difference among the groups in the period of experiment. Conclusion There is learning and memory impairment in the T3DM rats. P165 could raise the rats blood serum IGF-1 level, ameliorate learning and memory ability but did not influence the serum glucose.

Key words: analog of APP5mer peptide P165, rosiglitazone, type 3 diabetes, learning and memory ability, insulin-like growth factor-1