南方医科大学学报2016,Vol.36Issue(10):1345-1351,7.DOI:10.3969/j.issn.1673-4254.2016.10.08
胰高血糖素样多肽-1改善2型糖尿病大鼠的学习和记忆能力
Glucagon-like peptide 1 improves learning and memory abilities of rats with type 2 diabetes
摘要
Abstract
Objective To investigate the effect of glucagon-like peptide 1 (GLP-1) on cognitive dysfunction in diabetic rats. Methods Male SD rats were randomly divided into normal control group, diabetes mellitus (DM) group, and GLP-1 treatment group. Rat models of type 2 diabetes were established by high-sugar and high-fat feeding and streptozotocin (STZ) injection, and 25 days after the onset of diabetes, GLP-1 was infused in GLP-1 treatment group at the rate of 30 pmol · kg-1 · min-1 via a subcutaneous osmotic pump for 7 days. The learning and cognitive ability of the rats was assessed with Morris water maze test, and the expression of cognition-related genes in the hippocampus tissue was detected with real-time PCR, Western blotting and immunohistochemical staining. Results Compared with the normal control group, the diabetic rats showed significantly decreased learning and memory abilities (P<0.05) with increased hippocampal expressions of APP, BACE1, Arc, ERK1/2, PKA, and PKC mRNAs (P<0.05) and Arc protein. Compared with diabetic rats, GLP-1-treated rats showed significantly improvements in the learning and memory function (P<0.05) with decreased expressions of APP, BACE1, Arc, ERK1/2, and PKA mRNAs (P<0.05) and Arc protein. Conclusion GLP-1 can improve cognitive dysfunctions in diabetic rats possibly by regulating the PKC, PKA, and ERK1/2 pathways and inhibiting Arc expression in the hippocampus.关键词
胰高血糖素样多肽-1/糖尿病/学习与记忆功能障碍/ArcKey words
glucagon-like peptide 1/diabetes/cognitive dysfunction/Arc引用本文复制引用
谭照光,高维鸿,蔡祥胜,王方,惠宏襄..胰高血糖素样多肽-1改善2型糖尿病大鼠的学习和记忆能力[J].南方医科大学学报,2016,36(10):1345-1351,7.基金项目
国家973基金(2011CB504006);松山湖科技基金(2010B025,2010B026);广东科技基金(2010B090400041);博士点基金(20104433110014) Supported by National Key Basic Research Program (2011CB504006) (2010B090400041)