天然产物研究与开发 ›› 2019, Vol. 31 ›› Issue (7): 1246-1251.doi: 10.16333/j.1001-6880.2019.7.018

• 开发研究 • 上一篇    下一篇

四氢紫堇萨明对AD细胞模型Tau蛋白磷酸化的影响及其可能机制研究

姚兵,侯斌,李文燕,王志鑫,郭志方,康宁,冯炜,梁俊清*   

  1. 河北省中西医结合医药研究院,石家庄 050035
  • 出版日期:2019-07-29 发布日期:2019-07-29
  • 基金资助:

    国家自然科学基金青年基金( 81503231)

Effects and possible mechanisms of Tetrahydrocorysamine on phosphorylation of Tau in AD cell model

YAO Bing,HOU Bin,LI Wen-yan,WANG Zhi-xin, GUO Zhi-fang,KANG Ning,FENG Wei,LIANG Jun-qing*   

  1. Hebei Pharmaceutical Research Institute of Integrated Chinese and Western Medicine,Shijiazhuang 050035,China
  • Online:2019-07-29 Published:2019-07-29

摘要: 研究四氢紫堇萨明对Aβ25-35诱导的阿尔茨海默病细胞模型Tau蛋白磷酸化的影响及其可能作用机理。以神经细胞PC-12为载体,Aβ25-35诱导48 h建立AD细胞模型,MTS试剂盒检测细胞活力,激光共聚焦显微镜观察细胞核和细胞微管变化情况,Western blot法检测蛋白表达水平。结果显示,四氢紫堇萨明可显著增强模型细胞活力,改善微管形态,降低p-Tau(Ser396)和p-GSK-3β(Tyr216)表达水平,升高p-GSK-3β(Ser9)和p-AKT表达水平(P<0.05);PI3K抑制剂LY294002可部分阻断四氢紫堇萨明对模型细胞的上述改善作用。以上结果表明四氢紫堇萨明可显著改善AD细胞模型Tau蛋白过度磷酸化,从而改善细胞骨架微管形态,增强细胞活力,其机理可能与激活PI3K/Akt信号通路,降低GSK-3β活性,改善蛋白激酶/蛋白磷酸酯酶系统失衡相关。

关键词: 四氢紫堇萨明, A&beta, 25-35, PC-12, Tau

Abstract: To investigate the effect of tetrahydropyrimin (SQZJSM) on the phosphorylation of Tau protein in Alzheimers disease (AD) cell model and its possible mechanisms.AD cell model was established using PC-12 cell induced by Aβ25-35 for 48 h.Cell viability was detected by MTS,the changes of nuclei and microtubules were observed by laser confocal microscopy,the expression of protein was detected by Western blot.The results showed that SQZJSM can improve the cell viability and microtubule morphology of model cells,reduce the expression of p-Tau(Ser396) and p-GSK-3β(Tyr216) and up-regulate the expression of p-GSK-3β(Ser9) and p-AKT significantly (P<0.05).PI3K inhibitor LY294002 can partial block the improvement of SQZJSM on model cells.The above results indicate that tetrahydrocorysamine can significantly reduce the hyperphosphorylation of Tau protein in AD cell model,thereby improving the morphology of cytoskeletal microtubules and enhancing cell viability.The mechanism may be related to activating PI3K/Akt signaling pathway,decreasing GSK-3β activity and improving the imbalance of protein kinase/protein phosphatase system.

Key words: Tetrahydrocorysamine, A&beta, 25-35, PC-12, Tau

中图分类号: 

R966