天然产物研究与开发 ›› 2019, Vol. 31 ›› Issue (7): 1155-1162.doi: 10.16333/j.1001-6880.2019.7.006

• 研究论文 • 上一篇    下一篇

肉苁蓉苯乙醇苷对APP/PS1双转基因模型小鼠海马脑区β淀粉样蛋白表达的影响

居博伟1,杨建华2,胡君萍3*   

  1. 1新疆医科大学第五附属医院,乌鲁木齐830000;2新疆医科大学第一附属医院,乌鲁木齐830054;3新疆医科大学药学院,乌鲁木齐830011
  • 出版日期:2019-07-29 发布日期:2019-07-29
  • 基金资助:

    国家自然科学基金地区科学基金(81560629)

Effects of Cistanche deserticola phenylethanoside on the expression of β-amyloid protein in hippocampus of APP/PS1 transgenic mice

JU Bo-wei1,YANG Jian-hua2,HU Jun-ping3*   

  1. 1The Fifth affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China; 2The first affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China; 3School of Pharmacy,Xinjiang Medical University,Urumqi 830011,China
  • Online:2019-07-29 Published:2019-07-29

摘要: 为研究肉苁蓉苯乙醇苷对阿尔茨海默病模型小鼠海马β淀粉样蛋白表达的影响。实验选用6月龄APP/PS1双转基因AD模型小鼠60只,随机分为模型组、多奈哌齐组(0.65 mg/kg)、肉苁蓉苯乙醇总苷剂量组(250,125,62.5 mg/kg)、肉苁蓉毛蕊花糖苷组(125 mg/kg),正常组为同窝非转基因小鼠10只,分别给予药物和蒸馏水灌胃3个月,于9月龄时通过Morris水迷宫法检测行为学改变,采用HE染色法观察小鼠脑部海马病变,采用免疫组化法和Western-blot法考察海马Aβ1-42和Aβ1-40蛋白表达。实验结果发现肉苁蓉苯乙醇苷明显改善小鼠学习与记忆能力和脑部海马神经元的损伤,减少Aβ1-42、Aβ1-40阳性细胞数,并下调蛋白表达。肉苁蓉苯乙醇苷通过下调小鼠海马脑区Aβ1-42、Aβ1-40蛋白表达,从而影响Aβ级联反应以保护神经元,发挥拮抗AD作用。本研究明确了苯乙醇苷是肉苁蓉发挥抗AD活性的主要药效物质基础,为后续将其开发为抗AD新药提供了理论支撑。

关键词: 肉苁蓉, 苯乙醇苷, 阿尔茨海默病, APP/PS1双转基因小鼠, &beta, 淀粉样蛋白

Abstract: To study the effect of Cistanche deserticola phenylethanoside on the expression of β-amyloid protein in hippocampus of mice with Alzheimer disease,60 6-month-old APP/PS1 double-transgenic AD mice were randomly divided into modle groups,donepezil group (0.65 mg/kg),the high,middle,low dosages of total glycosides of Cistanche deserticola (250,125,62.5 mg/kg) and acteoside(125 mg/kg) were given drugs and distilled water for 3 months.At the age of 9 months,the Morris water maze and passive avoidance tests were used to determine the learning and memory impairments,the hippocampal lesions of mice were observed by HE staining,and the expressions of Aβ1-42 and Aβ1-40 proteins in hippocampus of mice were detected by immunohistochemical method and Western-blot method.Cistanche deserticola phenylethanoside can significantly improve the learning and memory ability and the damage of hippocampal neurons in APP/PS1 double transgenic mice.Compared with the model group,the number of Aβ1-42,Aβ1-40 positive cells in the hippocampus CA1 of the Cistanche deserticola group and the control group was significantly decreased,and the results of Western-blot showed that the expression of Aβ1-42,Aβ1-40 protein in hippocampus of Cistanche deserticola in each dose group and the intervention group was significantly lower than that in model group.Cistanche deserticola glycoside can protect neurons and antagonize AD by down-regulating the expression of Aβ1-42,Aβ1-40 protein in hippocampus brain of mice.In this study,phenylethanoside was identified as the main effective substance for Cistanche deserticola to exert its anti-AD activity,which provides theoretical support for its further development as a new drug against AD.

Key words: Cistanche deserticola, phenylethanoside, Alzheimer disease, APP/PS1 double transgenic mice, &beta, -amyloid protein

中图分类号: 

R285 R966