解剖学报

解剖学报 ›› 2020, Vol. 51 ›› Issue (2): 172-177.doi: 10.16098/j.issn.0529-1356.2020.02.004

• 神经生物学 • 上一篇    下一篇

丰富环境通过抑制NOD样受体蛋白3炎性小体活化缓解脂多糖小鼠的认知障碍

牛磊1 罗诗诗1 李威1 罗丹2 刘志文3 曹文宇1 徐杨4* 刘政海1*
  

  1. 1.南华大学衡阳医学院应用解剖学与生殖医学研究所，湖南 衡阳 421001； 2.南华大学衡阳医学院肿瘤研究所，湖南 衡阳 421001； 3.南华大学附属第二医院麻醉科，湖南 衡阳 421001； 4.南华大学衡阳医学院生理学教研室和神经科学研究所，湖南 衡阳 421001
  • 收稿日期:2019-01-23 修回日期:2019-03-16 出版日期:2020-04-06 发布日期:2020-04-06
  • 通讯作者: 徐杨;刘政海 E-mail:46926537@qq.com
  • 基金资助:
    湖南省自然科学基金青年基金项目;湖南省自然科学基金青年基金项目;湖南省自然科学基金省市联合基金项目;湖南省教育厅优秀青年项目;大学生研究性学习和创新实验设计计划项目

Environmental enrichment ameliorates lipopolysaccharide-induced cognitive impairment by  inhibiting NOD-like recepter protein 3 in fla mmasome activation in mice

NIU Lei1  LUO Shi-shi1  Li Wei1  Luo Dan2  LIU Zhi-wen3  CAO Wen-yu1  XU Yang4*  LIU Zheng-hai1*   

  1. 1.Clinical Anatomy and Reproductive Medicine Application Institute, School of Medicine, University of South China, Hunan Hengyang 421001, China; 2.Department of Pathology, Medical College, University of South China, Hunan Hengyang 421001, China; 3.Department of Anesthesiology, the Second Affiliated Hospital of University of South China, Hunan Hengyang 421001, China; 4.Department of Physiology and Institute of Neuroscience Medical School, University of South China, Hunan Hengyang 421001, China
  • Received:2019-01-23 Revised:2019-03-16 Online:2020-04-06 Published:2020-04-06
  • Contact: XU Yang;LIU Zheng-hai E-mail:46926537@qq.com

PDF

摘要：

目的 探讨丰富环境(EE)对脂多糖(LPS)诱导的小鼠认知功能障碍的影响及其可能机制。 方法 36只3周龄昆明小鼠进行8周的EE刺激或者标准环境（SE）饲养后分为以下3组：标准环境+生理盐水(SE+NS)组、标准环境+脂多糖(SE＋LPS)组及丰富环境+脂多糖(EE＋LPS)组。采用旷场实验检测小鼠的活动度；新旧事物识别实验检测小鼠认知功能；免疫组织化学方法检测小胶质细胞标记物离子钙接头蛋白分子1（IBA1）表达；Western blotting方法检测海马组织小胶质细胞激活标记物CD68及NOD样受体蛋白3(NOD-like receptor protein3, NLRP3)炎性小体相关蛋白的表达。 结果 旷场实验中，各组小鼠穿越的总格数无明显差异。在新旧事物识别实验中，与SE+NS组相比，SE+LPS组新事物辨别指数明显下降（P<0.05）；与SE+NS组相比，小胶质细胞标记物IBA1表达上调（P<0.05）；SE+LPS组海马CD68及NLRP3炎性小体相关蛋白的表达明显上调（P<0.05）；而丰富环境可以逆转上述改变（P<0.05）。 结论 丰富环境可缓解脂多糖诱导的认知功能损伤，其机制可能与抑制海马小胶质细胞激活及NLRP3炎性小体的产生有关。

关键词: 炎性小体, 脂多糖, 认知功能障碍, 小胶质细胞, 海马, 免疫印迹法, 小鼠

Abstract:

Objective  To investigate the effect of environmental enrichment (EE) on lipopolysaccharide (LPS) induced cognitive dysfunction in mice.  Methods A total of thirty six 3 weeks old Kunming mice experienced 8 weeks of EE or standard environment (SE) feeding. After 8 weeks, they were divided into three groups: standard environment+normal saline (SE+NS) group, standard environment+lipopolysaccharide (SE+LPS) group, environmental enrichment+lipopolysaccharide (EE+LPS) group. The open field test was used to measure the locomotive of mice, and the cognitive function was determined by novelty object recognition test. The expression of microglial marker ionized calcium binding adaptor molecule-1 (IBA-1) in hippocampus was determined by immunohistochemical staining. The expression of microglial activation marker CD68 and NOD-like receptor protein 3 (NLRP3) inflammasome related protein in the hippocampus was detected by Western blotting.  Results  In the open field test, there was no difference in the activity among the three groups. Compared with the SE＋NS group, SE＋LPS group showed decreased discrimination ratio in novelty object recognition task, with remarkably up-regulated expression of CD68 in the hippocampus (P<0.01). In addition, SE＋LPS group exhibited significantly enhanced expression of NLRP3, apoptosis associated speck-like protein (ASC), Caspase-1 and interleukin-1β(IL-1β) in the hippocampus compared with SE＋NS group (P<0.05). Compared with the SE＋LPS group, EE＋LPS group showed enhanced discrimination ratio in the object recognition task, with down-regulated expression of CD68, NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the hippocampus (P<0.01).   Conclusion  Environmental enrichment can alleviate LPS induced cognitive dysfunction, which might be attributed to the inhibiting of microglia and NLRP3 activation in the hippocampus.

Key words: Inflammasome, Lipopolysaccharide, Cognitive dysfunction, Microglia, Hippocampus, Western blotting, Mouse

中图分类号: