解剖学报 ›› 2020, Vol. 51 ›› Issue (1): 9-14.doi: 10.16098/j.issn.0529-1356.2020.01.002

• 神经生物学 • 上一篇    下一篇

海马sortilin在链脲佐菌素诱导的糖尿病认知损伤小鼠中的作用

罗丹1 杨惠1 罗诗诗2 牛磊2 李威2 宋光明2 谢靓哲2 徐杨3 曹文宇2* 何洁1*
  

  1. 1.南华大学衡阳医学院肿瘤研究所肿瘤细胞和分子病理学湖南省重点实验室; 2.应用解剖学与生殖医学研究所; 3.生理学教研室和神经科学研究所,湖南 衡阳 421001
  • 收稿日期:2019-02-27 修回日期:2019-06-10 出版日期:2020-02-06 发布日期:2020-04-21
  • 通讯作者: 曹文宇;何洁 E-mail:hejie430@126.com
  • 基金资助:
    自然科学基金青年基金项目;自然科学基金青年基金项目;自然科学基金省市联合基金项目;教育厅优秀青年项目;南华大学大学生研究性学习和创新性实验计划项目;南华大学大学生研究性学习和创新性实验计划项目

Role of hippocampal sortilin in streptozocin inducing diabetic cognitive impairment mice

LUO Dan1 YANG Hui1 LUO Shi-shi2 NIU Lei2 LI Wei2 SONG Guang-ming2 XIE Liang-zhe2 XU Yang3 CAO Wen-yu2* HE Jie1*   

  1. 1.Cancer Research Institute, Key Laboratory of Cancer Cellular and Molecular Pathology, Hengyang Medical College, University of South China, Hu’nan Hengyang 421001, China;  2.Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical College, University of South China, Hu’ nan Hengyang 421001, China;  3.Department of Physiology & Institute of Neuroscience, Hengyang Medical College, University of South China, Hu’nan Hengyang 421001, China 
  • Received:2019-02-27 Revised:2019-06-10 Online:2020-02-06 Published:2020-04-21
  • Contact: CAO Wen-yu;HE Jie E-mail:hejie430@126.com

摘要:

目的 探讨海马sortilin在链脲佐菌素(STZ)诱导的糖尿病认知损伤小鼠中的作用。方法 24只成年雄性ICR小鼠,随机分为溶媒对照组(NS)和实验组(STZ)。STZ腹腔注射诱导糖尿病认知损伤动物模型,注射后用血糖仪检测血糖改变,注射后第8周采用新旧事物识别实验检测各组小鼠认知功能;免疫组织化学方法检测sortilin免疫阳性产物表达变化;Western blotting和Real-time PCR方法检测各组小鼠海马sortilin和脑源性神经营养因子(BDNF)蛋白及mRNA表达变化。结果 与NS组相比,STZ组小鼠空腹血糖显著增高(P<0.01);在新旧事物识别实验中新事物辨别指数明显降低(P<0.05);海马区sortilin的免疫阳性产物(P<0.05)、蛋白(P<0.01)以及mRNA(P<0.05)表达均显著下调;海马区BDNF mRNA(P<0.01)及蛋白(P<0.05)表达均明显降低。结论 STZ诱导的糖尿病小鼠认知损伤可能与海马sortilin的表达下调有关。


关键词: 链脲佐菌素, 海马, 糖尿病, 认知损伤, Sortilin, 免疫组织化学, 小鼠

Abstract:

Objective To investigate the role of hippocampal sortilin in streptozotocin (STZ) inducing diabetic cognitive impairment in mice.

Methods Twenty four adult male ICR mice were randomly divided into control group (NS group) and experimental group (STZ group). The animal model of diabetic cognitive impairment was induced by STZ treatment. The blood glucose was measured by blood glucose meter every other week. The cognitive function was determined by novelty object recognition test 8 weeks after STZ injection. The expressions of sortilin in hippocampus of mice were determined by immunohistochemistry. The expressions of sortilin and brain-derived neurotrophic factor (BDNF)protein in hippocampus of mice were determined by Western blotting. The expressions of sortilin and BDNF mRNA in hippocampus of mice were determined by Real-time PCR. Results STZ treated mice showed significantly increased blood glucose compared with  the NS group (P<0.01). Compared with the NS group, the STZ group showed significantly reduced discrimination index in the novelty object recognition test (P<0.05). The result of immunohistochemistry assay showed that the positive score of NS group was significantly higher than STZ group (P<0.05).The results of Western blotting and Real-time PCR showed that the expression level of sortilin protein (P<0.01) and mRNA (P<0.05) in the hippocampus of STZ group decreased significantly compared with the NS group. The results of Western blotting and Real-time PCR showed that the expression level of BDNF protein (P<0.05) and mRNA (P<0.01) in the hippocampus of STZ group decreased significantly compared with the NS group.Conclusion The STZ-induced cognitive impairment in mice may be related to the down-regulation of sortilin in the hippocampus.


Key words: Streptozotocin, Hippocampus, Diabetes, Cognitive impairment, Sortilin, Immunohistochemistry, Mouse