天然产物研究与开发 ›› 2018, Vol. 30 ›› Issue (6): 958-963.doi: 10.16333/j.1001-6880.2018.6.007

• 研究论文 • 上一篇    下一篇

COX-2特异性抑制剂罗非昔布对阿尔茨海默病Aβ沉积的影响

王玥,于嵩,王旭*   

  1. 辽宁中医药大学解剖组胚教研室,沈阳 110847
  • 出版日期:2018-07-05 发布日期:2018-07-05
  • 基金资助:

    辽宁省自然科学基金(20170540604)

The Effects of COX-2 Specific Inhibitor Rofecoxib on the Deposition of A Beta in Alzheimer's Disease

WANG Yue,YU Song,WANG Xu*   

  1. Department of Tissue Culture,Liaoning University of Tradition Chinese Medicine,Shen Yang 110847,China
  • Online:2018-07-05 Published:2018-07-05

摘要: 本文应用免疫荧光、Western blot及ELISA等实验方法检测COX-2特异性抑制剂罗非昔布对阿尔茨海默病Aβ沉积的影响。实验分为三组,即对照组、AD模型组以及罗非昔布处理组。实验结果发现,与对照组小鼠相比,APP/PS1转基因小鼠脑内Aβ沉积及老年斑的数量增多、体积增大,Aβ1-40和Aβ1-42的含量增加,β-分泌酶和γ -分泌酶(包括BACE1、PS1、PS2、NCT)表达升高,并且小鼠脑内COX-2表达升高;小鼠经罗非昔布干预后,脑内Aβ沉积和老年斑数量减少、APP裂解酶和COX-2表达水平较AD模型组明显降低,以上结果说明COX-2特异性抑制剂罗非昔布可能通过抑制COX-2从而间接降低β-分泌酶和γ -分泌酶的活性,下调PS1、PS2、BACE1、NCT等分泌酶的表达,最终减少Aβ沉积和老年斑的形成,缓解阿尔茨海默病的发生与发展。

关键词: 阿尔茨海默病, APP/PS1转基因小鼠, 环氧合酶-2, 罗非昔布, &beta, -淀粉样蛋白, 老年斑, APP裂解酶

Abstract: In this study,we researched the effects of COX-2 specific inhibitor Rofecoxib on A beta deposition in Alzheimer's disease by immunofluorescence,Western blot and ELISA.The experiment was divided into three groups,that is wild type group,AD model group and Rofecoxib treatment group.The results showed that the number of A beta deposition and senile plaques increased,the volume enlarged compared with the wild type group,the contents of A beta 1-40 and A beta 1-42 increased,the expression of β-secretase and γ-secretase (including BACE1,PS1,PS2,NCT) elevated,and the expression of COX-2 in mouse brain increased.After treatment with Rofecoxib,A beta deposition and senile plaques decreased,the expression level of APP lyase and COX-2 were obviously lower than those in AD group.These results suggest that COX-2 specific inhibitor Rofecoxib could inhibit COX-2 expression,indirectly reduce β-secretase and γ-secretase activity,and downregulate PS1,PS2,BACE1 or NCT expressions,ultimately reduce the formation of A beta deposition and senile plaque,alleviate the occurrence and development of Alzheimer's disease.

Key words: Alzheimer’s disease, APP/PS1 transgenic mice, COX-2;Rofecoxib, Aβ, senile plaque, APP lyase

中图分类号: 

R285.5