D-半乳糖致认知障碍整体及离体模型的建立和评估

洪辰; 胡文君; 王淑娜; 李志勇; 缪朝玉

doi:10.3969/j.issn.1006-0111.2019.01.004

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

x 关闭永久关闭

《药学实践与服务》杂志目前不收取审稿费、版面费、加急费等费用，如收到邮件声称是编辑部X编辑，要求加作者微信的，请谨防财产损失！编辑部用于作者校对时绑定微信的邮件通过yxsjzzs@163.com发送，标题是《药学实践与服务》XML数字出版服务微信绑定，请区分开。

D-半乳糖致认知障碍整体及离体模型的建立和评估

洪辰, 胡文君, 王淑娜, 李志勇, 缪朝玉

文章导航 > 药学实践与服务 > 2019 > 37(1): 14-18,73

洪辰, 胡文君, 王淑娜, 李志勇, 缪朝玉. D-半乳糖致认知障碍整体及离体模型的建立和评估[J]. 药学实践与服务, 2019, 37(1): 14-18,73. doi: 10.3969/j.issn.1006-0111.2019.01.004

引用本文:

HUANG Jin-hua, MAO Gui-fu, WU Rong, LING Yi. Determination of chlorhexidine acetate in appliance-preserving solution by RP-HPLC[J]. Journal of Pharmaceutical Practice and Service, 2008, (1): 48-50.

Citation:

HONG Chen, HU Wenjun, WANG Shuna, LI Zhiyong, MIAO Chaoyu. Establishment and evaluation of in vivo and in vitro D-galactose induced cognitive impairment models[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(1): 14-18,73. doi: 10.3969/j.issn.1006-0111.2019.01.004

D-半乳糖致认知障碍整体及离体模型的建立和评估

doi: 10.3969/j.issn.1006-0111.2019.01.004

海军军医大学药学院药理学教研室, 上海 200433

基金项目: 国家自然科学基金重点项目（81730098）

Establishment and evaluation of in vivo and in vitro D-galactose induced cognitive impairment models

Department of Pharmacology, School of Pharmacy, Naval Medical University, Shanghai 200433, China

摘要: 目的通过构建D-半乳糖［D-（+）galactose，D-gal］致认知障碍的整体及离体模型，并检测两种模型的相关指标，探索两种模型的建立方法，并评估联合应用D-gal整体及离体模型的应用价值和前景。方法采用连续腹腔注射D-gal生理盐水溶液8周制备D-gal致认知障碍整体动物模型，并采用Morris水迷宫评价小鼠的学习和记忆功能，之后检测脑组织中相关的分子指标评估模型效果；采用外源性给予体外培养的幼鼠海马区神经元细胞D-gal制备D-gal细胞模型，并检测细胞损伤的相关分子指标，评估离体模型效果和应用价值。结果在D-gal模型下的Morris水迷宫实验结果显示，模型组动物的学习和记忆功能显著低于对照组动物，与此同时，模型组动物的神经元凋亡和氧化应激水平明显高于对照组动物；D-gal海马区神经元细胞模型中显示，随着D-gal剂量的增加，神经元细胞出现功能和形态学改变，其凋亡和氧化应激水平明显高于对照组神经元细胞。结论 D-gal致认知障碍整体模型及在离体状态下给予海马区神经元细胞D-gal均可以诱发细胞凋亡和氧化应激损伤，并导致动物学习和记忆功能下降；联合应用D-gal致认知障碍整体及离体模型可以成为今后研究认知障碍机制和药效学评价的有效模型之一。
- D-半乳糖 /
- 认知功能 /
- Morris水迷宫 /
- 海马神经元
Abstract: Objective To construct and explore the in vivo and in vitro D-galactose induced cognitive impairment models and evaluate the application value of the combined models in the study of cognitive impairments. Methods The cognitive impairment mice model induced by D-gal was prepared by continuous intraperitoneal injection of D-gal saline solution for 8 weeks, followed by detection of learning and memory functions with Morris water maze. The related molecular markers in the brain tissue were assayed to evaluate the effect and application value. D-gal cell model was prepared by adding D-gal in different concentrations into the cell cultural medium of neurons harvested from the hippocampus of young mice. The effect and application value were evaluated by detecting the molecular markers related to the level of cell injury. Results The Morris water maze on the D-gal model showed that the learning and memory functions of mice in the model group were significantly lower than those in the control group. Meanwhile, the levels of apoptosis and oxidative stress in the model group were significantly higher than those in the control group. In the hippocampal neuron model of D-gal, the neurons showed a dose-dependent morphologic and functional change with the increase of D-gal dose and the levels of apoptosis and oxidative stress were significantly higher than those in the negative control. Conclusion D-galactose can be successfully used to induce cognitive impairment models both in vivo and in vitro through the decrease of the learning and memory functions of mice and induction of apoptosis and oxidative stress in neurons. Combined application of the two models of D-gal can be one of effective and promising tools for the study of cognitive impairment and pharmacodynamic evaluation.
- D-galactose /
- cognitive function /
- Morris water maze /
- hippocampus neuron

[1]	MIQUEL S, CHAMP C, DAY J, et al. Poor cognitive ageing:vulnerabilities, mechanisms and the impact of nutritional interventions[J]. Ageing Res Rev, 2018, 42:40-55.
[2]	CHAN K Y, WANG W, WU J J, et al. Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990-2010:a systematic review and analysis[J]. Lancet, 2013, 381(9882):2016-2023.
[3]	KANG E, WEN Z, SONG H, et al. Adult neurogenesis and psychiatric disorders[J]. Cold Spring Harb Perspect Biol, 2016, 8(9):a019026.
[4]	ERNST A, ALKASS K, BERNARD S, et al. Neurogenesis in the striatum of the adult human brain[J]. Cell, 2014, 156(5):1072-1083.
[5]	ALI T, BADSHAH H, KIM T H, et al. Melatonin attenuates D-galactose-induced memory impairment, neuroinflammation and neurodegeneration via RAGE/NF-K B/JNK signaling pathway in aging mouse model[J]. J Pineal Res, 2015, 58(1):71-85.
[6]	VORHEES C V, WILLIAMS M T. Morris water maze:procedures for assessing spatial and related forms of learning and memory[J]. Nat Protoc, 2006, 1(2):848-858.
[7]	MIYAMOTO T, STEIN L, THOMAS R, et al. Phosphorylation of tau at Y18, but not tau-fyn binding, is required for tau to modulate NMDA receptor-dependent excitotoxicity in primary neuronal culture[J]. Molecul Neurodegen, 2017, 12(1):41.
[8]	HUSAIN M, MEHTA M A. Cognitive enhancement by drugs in health and disease[J]. Trends Cogn Sci (Regul Ed), 2011, 15(1):28-36.
[9]	SHWE T, PRATCHAYASAKUL W, CHATTIPAKORN N, et al. Role of D-galactose-induced brain aging and its potential used for therapeutic interventions[J]. Exp Gerontol, 2017, 101:13-36.
[10]	WEI H, LI L, SONG Q, et al. Behavioural study of the D-galactose induced aging model in C57BL/6J mice.[J]. Behav Brain Res, 2005, 157(2):245-251.
[11]	SADIGHETEGHAD S, MAJDI A, MCCANN S K, et al. D-galactose-induced brain ageing model:a systematic review and Meta-analysis on cognitive outcomes and oxidative stress indices[J]. Plos One, 2017, 12(8):e0184122.

[1]	迟文雅, 袁艳, 李伟林, 吴茼妤, 俞媛. 负载骨髓间充质干细胞/白藜芦醇脂质体的水凝胶支架治疗创伤性脑损伤的研究 . 药学实践与服务, 2025, 43(2): 67-74. doi: 10.12206/j.issn.2097-2024.202406034
[2]	冯一帆, 严啸东, 张文彬, 李炳锋, 郭美丽. 菸花苷长期给药对脑缺血再灌注损伤大鼠神经功能的影响 . 药学实践与服务, 2025, 43(): 1-7. doi: 10.12206/j.issn.2097-2024.202407038
[3]	张俊丽, 李媛媛, 尹静, 杨鸿源, 白耀武. 咪达唑仑调节PINK1/PARKIN信号通路对缺血性脑卒中大鼠神经元损伤的影响 . 药学实践与服务, 2025, 43(): 1-6. doi: 10.12206/j.issn.2097-2024.202405024
[4]	石晓萍, 吕迁洲, 李晓宇, 许青. 泊沙康唑对比伏立康唑经验治疗或诊断驱动治疗免疫功能低下患者侵袭性霉菌病的成本-效果分析 . 药学实践与服务, 2024, 42(12): 512-519. doi: 10.12206/j.issn.2097-2024.202401050
[5]	邹思, 吴岩斌, 吴锦忠, 吴建国, 黄家兴. 虎奶菇菌核多糖功能化纳米硒抗疲劳功效研究 . 药学实践与服务, 2024, 42(10): 426-432. doi: 10.12206/j.issn.2097-2024.202206072

点击查看大图

计量

文章访问数: 4075
HTML全文浏览量: 664
PDF下载量: 477
被引次数: 0

D-半乳糖致认知障碍整体及离体模型的建立和评估

doi: 10.3969/j.issn.1006-0111.2019.01.004

海军军医大学药学院药理学教研室, 上海 200433

基金项目: 国家自然科学基金重点项目（81730098）

收稿日期: 2018-07-02
修回日期: 2018-09-12

关键词:

D-半乳糖 /

认知功能 /

Morris水迷宫 /

海马神经元

摘要: 目的通过构建D-半乳糖［D-（+）galactose，D-gal］致认知障碍的整体及离体模型，并检测两种模型的相关指标，探索两种模型的建立方法，并评估联合应用D-gal整体及离体模型的应用价值和前景。方法采用连续腹腔注射D-gal生理盐水溶液8周制备D-gal致认知障碍整体动物模型，并采用Morris水迷宫评价小鼠的学习和记忆功能，之后检测脑组织中相关的分子指标评估模型效果；采用外源性给予体外培养的幼鼠海马区神经元细胞D-gal制备D-gal细胞模型，并检测细胞损伤的相关分子指标，评估离体模型效果和应用价值。结果在D-gal模型下的Morris水迷宫实验结果显示，模型组动物的学习和记忆功能显著低于对照组动物，与此同时，模型组动物的神经元凋亡和氧化应激水平明显高于对照组动物；D-gal海马区神经元细胞模型中显示，随着D-gal剂量的增加，神经元细胞出现功能和形态学改变，其凋亡和氧化应激水平明显高于对照组神经元细胞。结论 D-gal致认知障碍整体模型及在离体状态下给予海马区神经元细胞D-gal均可以诱发细胞凋亡和氧化应激损伤，并导致动物学习和记忆功能下降；联合应用D-gal致认知障碍整体及离体模型可以成为今后研究认知障碍机制和药效学评价的有效模型之一。

English Abstract

Establishment and evaluation of in vivo and in vitro D-galactose induced cognitive impairment models

Department of Pharmacology, School of Pharmacy, Naval Medical University, Shanghai 200433, China

Received Date: 2018-07-02
Rev Recd Date: 2018-09-12

Keywords:

Abstract: Objective To construct and explore the in vivo and in vitro D-galactose induced cognitive impairment models and evaluate the application value of the combined models in the study of cognitive impairments. Methods The cognitive impairment mice model induced by D-gal was prepared by continuous intraperitoneal injection of D-gal saline solution for 8 weeks, followed by detection of learning and memory functions with Morris water maze. The related molecular markers in the brain tissue were assayed to evaluate the effect and application value. D-gal cell model was prepared by adding D-gal in different concentrations into the cell cultural medium of neurons harvested from the hippocampus of young mice. The effect and application value were evaluated by detecting the molecular markers related to the level of cell injury. Results The Morris water maze on the D-gal model showed that the learning and memory functions of mice in the model group were significantly lower than those in the control group. Meanwhile, the levels of apoptosis and oxidative stress in the model group were significantly higher than those in the control group. In the hippocampal neuron model of D-gal, the neurons showed a dose-dependent morphologic and functional change with the increase of D-gal dose and the levels of apoptosis and oxidative stress were significantly higher than those in the negative control. Conclusion D-galactose can be successfully used to induce cognitive impairment models both in vivo and in vitro through the decrease of the learning and memory functions of mice and induction of apoptosis and oxidative stress in neurons. Combined application of the two models of D-gal can be one of effective and promising tools for the study of cognitive impairment and pharmacodynamic evaluation.

引用本文:

HUANG Jin-hua, MAO Gui-fu, WU Rong, LING Yi. Determination of chlorhexidine acetate in appliance-preserving solution by RP-HPLC[J]. Journal of Pharmaceutical Practice and Service, 2008, (1): 48-50.

Citation: