中国药物警戒 ›› 2017, Vol. 14 ›› Issue (10): 577-581.

• 基础与临床研究 •    下一篇

瓜子金皂苷己在小鼠中抗淀粉样蛋白损伤的作用与机制

高卫真1, 穆鑫2, 张晓华1*   

  1. 1.上海交通大学医学院附属仁济医院神经外科，上海200127;
    2.中国医学科学院药物研究所，北京100050
  • 收稿日期:2017-09-22 修回日期:2017-11-30 出版日期:2017-10-20 发布日期:2017-11-30
  • 通讯作者: 张晓华，男，博士，主任医师·博导，复杂性脑肿瘤和脑血管疾病。E-mail：zxh1969@aliyun.com
  • 作者简介:高卫真，男，硕士，主治医师，脑肿瘤的手术及综合治疗。

Function and Mechanism of Polygalasaponin F on Amyloid β Protein-induced Damage in Mice

GAO Wei-zhen1,MU Xin2,ZHANG Xiao-hua1*   

  1. 1.Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China;
    2.Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • Received:2017-09-22 Revised:2017-11-30 Online:2017-10-20 Published:2017-11-30

PDF (PC)

133

摘要： 目的 研究瓜子金皂苷己（polygalasaponin F，PGSF）抗淀粉样蛋白（amyloid β，Aβ）损伤的作用与机制。方法 利用Aβ损伤PC12细胞，噻唑蓝（3-（4,5-dimethyhhyhhiazol-2-y1）-2,5-diphenyhetrazolium bromide，MTT）检测细胞存活率，DCFH-DA探针检测细胞内活性氧自由基，海马注Aβ后，利用Morris水迷宫评价动物认知行为学的改变，Western blot方法检测学习记忆相关蛋白的变化。结果 体外实验结果显示，Aβ 能够抑制PC12细胞存活率，并促进细胞内活性氧的堆积；海马注射Aβ后，模型动物的逃避潜伏期延长，穿越目标象限的次数减少，而PGSF高剂量（20 mg kg-1）对上述学习记忆障碍的行为具有改善功能。蛋白检测发现PGSF能够增加脑源性神经营养因子（BDNF）的水平，促进受体酪氨酸激酶和GSK3β 216位点酪氨酸的磷酸化。结论 PGSF能够减轻Aβ对神经细胞的损伤，改善学习记忆，其作用机制可能与RTK-GSK3 -BDNF信号传导通路有关，是具有治疗老年痴呆潜能的化合物。

关键词: 瓜子金皂苷己, 淀粉样蛋白, 老年痴呆, 脑源性神经营养因子（BDNF）

Abstract: Objective To study the protective function and mechanism of polygalasaponin F(PGSF) against the injury induced by amyloid β protein (Aβ). Methods PC12 cells were exposed to Aβ, and the cell viability was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT), the accumulation of intracellular reactive oxygen species(ROS) were measured by DCFH-DA probe, the effects of PGSF on cognition were evaluated through the Morris water maze, and the protein level was detected by Western blot methods. Results It was showed that PGSF could increase the cell viability-impaired by Aβ, and decrease the accumulation of ROS induced by Aβ. Results further showed that Aβ could prolong the escape latency and decrease the crossing frequency, and PGSF (20 mg·kg-1) could improve these impaired movements. PGSF also could increase the protein level of brain derived neurophic factor(BDNF), and enhance the phosphorylation of TRK and GSK3β 216Y. Conclusion PGSF could protect cells from Aβ damage, and it was proved to prevent A-destroyed learning and memory, and this function might be associated with TRK-GSK3β-BDNF signal pathway. So, PGSF might be apotential compound for Alzheimer's disease.

Key words: polygalasaponin F, amyloid β protein, Alzheimer's disease, brain derived neurophic factor (BDNF)

中图分类号: