南方医科大学学报2018，Vol.38Issue(4)：384-389,6.DOI:10.3969/j.issn.1673-4254.2018.04.03
尼可地尔可改善链脲佐菌素诱导的糖尿病小鼠的认知功能障碍
Nicorandil improves cognitive dysfunction in mice with streptozotocin-induced diabetes
摘要
Abstract
Objective To observe the protective effects of potassium channel opener nicorandil against cognitive dysfunction in mice with streptozotocin(STZ)-induced diabetes.Methods C57BL/6J mouse models of type 1 diabetes mellitus(T1DM)were established by intraperitoneal injection of STZ and received daily treatment with intragastric administration of nicorandil or saline(model group)for 4 consecutive weeks,with normal C57BL/6J mice serving as control.Fasting blood glucose level was recorded every week and Morris water maze was used to evaluate the cognitive behavior of the mice in the 4th week.At the end of the experiment,the mice were sacrificed to observe the ultrastructural changes in the hippocampus and pancreas under transmission electron microscopy; the contents of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the hippocampus and SOD activity and MDA level in the brain tissue were determined. Results Compared with the control group, the model group showed significantly increased fasting blood glucose (P<0.001), significantly prolonged escape latency (P<0.05) and increased swimming distance (P<0.01) with ultrastructural damage of pancreatic β cells and in the hippocampus;GIP and GLP-1 contents in the hippocampus(P<0.01)and SOD activity in the brain were significantly decreased (P<0.05) and MDA content was significantly increased in the model group (P<0.05). Compared with the model group, nicorandil treatment did not cause significant changes in fasting blood glucose, but significantly reduced the swimming distance (P<0.05); nicorandil did not improve the ultrastructural changes in pancreatic β cells but obviously improved the ultrastructures of hippocampal neurons and synapses. Nicorandil also significantly increased the contents of GIP and GLP-1 in the hippocampus(P<0.05),enhanced SOD activity(P<0.05)and decreased MDA level(P<0.01)in the brain tissue.Conclusion Nicorandil improves cognitive dysfunction in mice with STZ-induced diabetes by increasing GIP and GLP-1 contents in the hippocampus and promoting antioxidation to relieve hippocampal injury.关键词
尼可地尔/糖尿病认知功能障碍/海马/肠促胰岛素/氧化应激Key words
nicorandil/diabetic cognitive dysfunction/hippocampus/incretin/oxidative stress引用本文复制引用
颜文慧,张萌,陈莉娜,张纯茜,邢通,宫雪,杨宇轩,李亦诺,刘玄,阿依江·加马力丁,郁叶..尼可地尔可改善链脲佐菌素诱导的糖尿病小鼠的认知功能障碍[J].南方医科大学学报,2018,38(4):384-389,6.基金项目
国家自然科学基金(81471031) （81471031）
西安交通大学本科生科研训练和实践创新基金项目(XJ201610698083)Supported by National Natural Science Foundation of China(81471031). （XJ201610698083）
