南方医科大学学报

南方医科大学学报 ›› 2018, Vol. 38 ›› Issue (04): 384-.

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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

颜文慧，张纯茜，邢通，宫雪，杨宇轩，李亦诺，刘玄，阿依江·加马力丁，郁叶，张萌，陈莉娜   

  • 出版日期:2018-04-20 发布日期:2018-04-20

Nicorandil improves cognitive dysfunction in mice with streptozotocin-induced diabetes

  • Online:2018-04-20 Published:2018-04-20

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摘要： 目的研究钾通道开放剂尼可地尔对链脲佐菌素（STZ）诱导的糖尿病小鼠认知功能障碍的保护作用。方法对C57BL/6J 小鼠采用STZ诱导1型糖尿病，实验分为正常组、模型组和尼可地尔组。每周记录空腹血糖变化情况；第4周Morris水迷宫检测 小鼠认知行为；处死后，取小鼠海马和胰腺组织进行透射电镜观察，检测海马组织中肠促胰岛素葡萄糖依赖性促胰岛素多肽 （GIP）和胰高血糖素样肽-1（GLP-1）的含量，及脑组织超氧化物歧化酶（SOD）活力和丙二醛（MDA）含量。结果与正常组相比， 模型组小鼠空腹血糖明显升高（P<0.001），逃避潜伏期延长（P<0.05），游泳距离增加（P<0.01）；胰腺β细胞和海马超微结构受损； 海马组织中GIP和GLP-1含量降低（P<0.01），脑组织中SOD活力下降（P<0.05），MDA含量升高（P<0.05）。与模型组相比，尼可 地尔对空腹血糖无影响，可降低游泳距离（P<0.05）；对胰腺β细胞无明显改善，但可改善海马神经元以及突触的超微结构；可增 加糖尿病小鼠脑组织中GIP和GLP-1的含量（P<0.05），增强脑组织中的SOD活力（P<0.05），降低MDA含量（P<0.01）。结论尼 可地尔可通过提高海马中GIP和GLP-1含量，及抗氧化作用，缓解海马结构损伤，改善STZ诱导的糖尿病认知功能障碍。

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.