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海马内不同亚型雌激素受体α及相关信号分子与糖尿病小鼠空间认知障碍的相关性

张明睿, 屈超, 孙佳, 王翠, 李洪艳, 张叶军, 张炳强, 邹伟

辽宁师范大学生命科学学院，大连 116081；大连市中心医院神经内科，大连 116033；卫生部细胞移植重点实验室临床中心，青岛 266100；中国人民解放军第二一零医院，大连 116021

摘要

本研究旨在探讨海马内不同亚型雌激素受体α (estrogen receptor α, ERα)及相关信号分子与糖尿病引起的空间认知障碍的相关性。腹腔注射四氧嘧啶建立1型糖尿病小鼠模型，并采用Morris水迷宫方法检测模型组小鼠是否存在空间认知障碍；然后用Western blot比较模型组和正常对照组小鼠海马内ERα不同亚型ER-α36和ER-α66的表达，同时检测窖蛋白-1 (caveolin-1)、PKCα、cAMP反应元件结合蛋白2 (cAMP-response element binding protein 2, CREB2)和突触素(synaptophysin, Syn)的表达变化。结果显示，相对对照组，糖尿病模型组小鼠空间训练第3天和第5天的逃避潜伏期显著延长(P < 0.05)，撤去平台后游泳路程增加；模型组小鼠海马caveolin-1、PKCα表达量显著降低(P < 0.05)，ER-α66蛋白表达水平没有明显变化，而ER-α36和CREB2的表达量显著升高(P < 0.05)。以上结果提示，海马内ER-α36及相关信号分子的异常表达对糖尿病小鼠空间认知障碍形成可能具有重要的作用。

关键词： 空间学习记忆; 雌激素受体α ; 糖尿病 ; 认知障碍

分类号：Q4

Different subtypes of estrogen receptor α and related signal molecules in the hippocampus are associated with spatial cognitive impairment of diabetic mice

ZHANG Ming-Rui, QU Chao, SUN Jia, WANG Cui, LI Hong-Yan, ZHANG Ye-Jun, ZHANG Bing-Qiang, ZOU Wei

College of Life Science, Liaoning Normal University, Dalian 116081, China； Department of Neurology, Central Hospital of Dalian, Dalian 116033, China； The Key Laboratory of Cell Transplantation, Health Clinical Center of Ministry, Qingdao 266100, China； The 210th Hospital of PLA, Dalian 116021, China

Abstract

To study the correlation between the spatial cognitive impairment and different subtypes of estrogen receptor α (ERα) of hippocampus in diabetic mice, we used alloxan (intraperitoneal injection) to induce type 1 diabetes in male Kunming mice and compared the spatial cognitive ability of the model mice with that of control mice through Morris water maze test. Meanwhile, using Western blot, we detected the protein expressions of ER-α36, ER-α66, caveolin-1, PKCα, cAMP-response element binding protein 2 (CREB2), and synaptophysin (Syn) in the hippocampus of the mice. The results showed that on the 3rd and 5th days of training, the ability of spatial learning and memory in the diabetic mice was significantly inferior to that of the control mice (P < 0.05). In the diabetic mice, the protein expressions of caveolin-1 and PKCα were decreased (P < 0.05), but ER-α66 expression was unaffected, while ER-α36 and CREB2 expressions were significantly increased (P < 0.05) compared with those of the control mice. The results suggest that abnormal expression of ER-α36 and related signal molecules may be important factors for diabetes-induced spatial cognitive impairment.

Key words: Spatial learning and memory; estrogen receptor α ; diabetes ; spatial cognitive impairment

收稿日期：2016-10-11　　录用日期：2017-02-24

通讯作者：邹伟　　E-mail: weizou60@126.com

引用本文：

张明睿, 屈超, 孙佳, 王翠, 李洪艳, 张叶军, 张炳强, 邹伟. 海马内不同亚型雌激素受体α及相关信号分子与糖尿病小鼠空间认知障碍的相关性[J]. 生理学报 2017; 69 (3): 252-260.

ZHANG Ming-Rui, QU Chao, SUN Jia, WANG Cui, LI Hong-Yan, ZHANG Ye-Jun, ZHANG Bing-Qiang, ZOU Wei. Different subtypes of estrogen receptor α and related signal molecules in the hippocampus are associated with spatial cognitive impairment of diabetic mice. Acta Physiol Sin 2017; 69 (3): 252-260 (in Chinese with English abstract).