动物造模 z-bio 2022-07-20 349

　　Objective: To observe the improvement effect of diabetes treatment drug glucagon-like peptide-1 (GLP-1) on learning and memory dysfunction in diabetic rats.

　　Methods: Male SD rats were randomly divided into normal group (Normal), diabetes model group (DM) and GLP-1 treatment group (GLP-1). A type 2 diabetes model was established by high-fat and high-glucose feeding combined with streptozotocin (STZ) induction. The diabetic rat models were randomly divided into the diabetes group and the GLP-1 group. The rats in the diabetes group were not treated, and the rats in the GLP-1 group were given GLP-1 by subcutaneously embedded sustained-release pump on the 25th day after the formation of diabetes. (30 pmol/kg/min) for 7 days. After the treatment, the Morris water maze test was used to evaluate the learning and cognitive ability of the rats in each group, and then the hippocampus tissue of the rat brain was obtained. Western blotting was used to detect the expression of cognitive-related proteins, and immunohistochemistry was used to detect the expression and cellular localization of cognitive-related proteins.

　　Results: Morris water maze test showed that the learning and memory functions of diabetic rats were significantly decreased (P<0.05). Real-time quantitative PCR showed that the gene transcription of APP, BACE1, Arc, ERK1/2, PKA, PKC in the brain of diabetic rats increased (P<0.05), Western Blotting and immunohistochemical results showed that the expression of Arc protein molecules increased in diabetic rats. However, the learning and memory functions of the GLP-1-treated rats were significantly improved than those of the diabetes group (P<0.05), and the transcriptional expressions of APP, BACE1, Arc, ERK1/2, PKA, and PKC genes in the brain were significantly decreased (P<0.05). , Arc expression decreased.

　　Conclusion: GLP-1 treatment can significantly improve the learning and memory dysfunction in type 2 diabetic rats, and its effect may be achieved by regulating the PKC, PKA, ERK1/2 pathways of cells and inhibiting the expression of Arc.