五味子木脂素改善衰老小鼠学习记忆能力的机制

郭笑; 叶玉洁; 宋昆; 安丽萍; 盛瑜

doi:10.13422/j.cnki.syfjx.20201226

您当前的位置：

首页 >

文章列表页 >

五味子木脂素改善衰老小鼠学习记忆能力的机制

药理 | 更新时间：2020-09-09

- 五味子木脂素改善衰老小鼠学习记忆能力的机制
- Mechanism of Schisandrae Chinensis Fructus Lignans in Alleviating Learning and Memory Ability in D-galactose Aging Mice
- 中国实验方剂学杂志 2020年26卷第14期页码：85-91
- 作者机构：
  
  北华大学药学院，吉林吉林 132013
- 作者简介：
  
  郭笑，博士，讲师，从事分子生物学研究，E-mail：395798544@qq.com
  盛瑜，博士，讲师，从事药物分析研究，Tel：0432-64608008，E-mail：383165810@qq.com
- 基金信息：
  
  国家自然科学基金项目(31900918);吉林省教育厅“十三五”科学技术项目(JJKH20180374KJ);吉林省科技发展计划项目(20170311039YY;20180520051JH);吉林省卫生健康青年科技骨干培养计划项目(2019Q020)
- DOI：10.13422/j.cnki.syfjx.20201226
  中图分类号： R22;R242;R2-031;R285.5
- 网络出版日期：2020-04-15，
  
  纸质出版日期：2020-07-20
- 稿件说明：
移动端阅览
郭笑,叶玉洁,宋昆等.五味子木脂素改善衰老小鼠学习记忆能力的机制[J].中国实验方剂学杂志,2020,26(14):85-91.

GUO Xiao,YE Yu-jie,SONG Kun,et al.Mechanism of Schisandrae Chinensis Fructus Lignans in Alleviating Learning and Memory Ability in D-galactose Aging Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(14):85-91.
郭笑,叶玉洁,宋昆等.五味子木脂素改善衰老小鼠学习记忆能力的机制[J].中国实验方剂学杂志,2020,26(14):85-91. DOI： 10.13422/j.cnki.syfjx.20201226.

GUO Xiao,YE Yu-jie,SONG Kun,et al.Mechanism of Schisandrae Chinensis Fructus Lignans in Alleviating Learning and Memory Ability in D-galactose Aging Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(14):85-91. DOI： 10.13422/j.cnki.syfjx.20201226.

摘要

目的

研究五味子木脂素（Schisandrae Chinensis Fructus lignans，SCL）对

-半乳糖（

-galactose，

-gal）所致衰老模型小鼠学习记忆能力的改善作用。

方法

ICR小鼠随机分为4组，即正常组（灌胃蒸馏水，皮下注射生理盐水），模型组（灌胃蒸馏水，皮下注射200 mg·kg

-1

·d

-1

-gal），吡拉西坦组（灌胃吡拉西坦200 mg·kg

-1

·d

-1

，皮下注射

-gal 200 mg·kg

-1

·d

-1

），SCL低剂量组（灌胃SCL 50 mg·kg

-1

·d

-1

，皮下注射

-gal 200 mg·kg

-1

·d

-1

），SCL中剂量组（灌胃SCL 100 mg·kg

-1

·d

-1

，皮下注射

-gal 200 mg·kg

-1

·d

-1

），SCL高剂量组（灌胃SCL 200 mg·kg

-1

·d

-1

，皮下注射

-gal 200 mg·kg

-1

·d

-1

），连续给药10周；通过避暗实验及Morris水迷宫实验观察SCL对

-gal致衰老模型小鼠学习记忆能力的影响；通过化学比色法检测小鼠脑组织中超氧化物歧化酶（superoxide dismutase，SOD）活力及丙二醛（malondialdehyde，MDA）含量；通过聚合酶链式反应（polymerase chain reaction，PCR）检测小鼠脑组织中过氧化物还原酶-6（peroxiredoxin-6，Prdx6），谷胱甘肽过氧化酶1（glutathione peroxidase 1，GSH-Px1）mRNA表达情况；蛋白免疫印迹法（Western blot）检测小鼠组织中Prdx6，GSH-Px1蛋白表达情况。

结果

行为学实验中，与正常组比较，模型组小鼠避暗错误次数明显增加（

0.05），潜伏期显著减少（

0.01），小鼠穿台次数和目标象限停留时间显著减少（

0.01），可作为建模成功的指标。与模型组比较，吡拉西坦组，SCL中、高剂量组小鼠避暗错误次数明显减少（

0.05，

0.01），潜伏期明显延长（

0.05，

0.01），同时，SCL高剂量组小鼠水迷宫穿台次数和目标象限停留时间显著增加（

0.01）。与正常组比较，模型组小鼠脑组织中的SOD活力显著降低（

0.01），MDA含量增加（

0.05），Prdx6，GSH-Px1 mRNA及蛋白表达量明显下降（

0.05，

0.01）。与模型组比较，吡拉西坦组，SCL低、中、高剂量组小鼠脑组织中SOD活力增高（

0.05），MDA水平降低（

0.05），Prdx6，GSH-Px1 mRNA及蛋白的表达水平显著升高（

0.05，

0.01），说明SCL给药组具有剂量依赖性。

结论

SCL能改善

-gal致衰老模型小鼠学习记忆能力，该作用可能与SCL提高小鼠抗氧化能力及上调小鼠脑组织中Prdx6，GSH-Px1的表达水平有关。

Abstract

Objective

To study the effect of Schisandrae Chinensis Fructus lignans (SCL) on learning and memory ability of

-galactose（

-gal）-induced aging model mice.

Method

ICR mice were randomly divided into 4 groups: normal group (distilled water

subcutaneous injection with normal saline)

model group (distilled water

subcutaneous injection with 200 mg·kg

-1

-gal)

piracetam group (oral administration with 200 mg·kg

-1

piracetam

subcutaneous injection with 200 mg·kg

-1

-gal)

low-dose SCL group (oral administration with 50 mg·kg

-1

·d

-1

SCL

subcutaneous injection with 200 mg·kg

-1

·d

-1

-gal)

medium-dose SCL group (oral administration with 100 mg·kg

-1

·d

-1

SCL

subcutaneous injection with 200 mg·kg

-1

·d

-1

-gal)

high-dose SCL group (oral administration with 200 mg·kg

-1

·d

-1

SCL

subcutaneous injection with 200 mg·kg

-1

·d

-1

-gal). The drugs were administered continuously for 10 weeks. Dark test and Morris water maze test were performed to observe the effect of SCL on the learning and memory ability of

-gal-induced aging mice. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in mouse brain tissue were detected by chemical colorimetry. The expressions of peroxiredoxin-6（Prdx6） and glutathione peroxidase 1（GSH-Px1） mRNA in mouse brain tissue were detected by polymerase chain reaction (PCR). The expressions of Prdx6 and GSH-Px1 protein in mouse tissues were detected by Western blot.

Result

In behavioral experiments

compared with normal group

the number of dark avoidance errors in model group significantly increased (

0.05)

the latency was significantly reduced (

0.01)

and the number of mouse passes and the target quadrant residence time were significantly reduced (

0.01)

which can be used as an indicator of successful modeling. Compared with the model group

the number of errors in the piracetam group

and medium and high-dose SCL groups was significantly reduced (

0.05，

0.01)

and the latency was significantly prolonged (

0.05，

0.01). At the same time

the number of water maze passes and the target quadrant retention time in the high-dose SCL group increased significantly (

0.01). The results of biochemical indicators showed that compared with normal group

the SOD activity in brain tissue of model group mice was significantly reduced (

0.01)

while the MDA content was increased (

0.05). Compared with the model group

SOD activity in the brain tissues of piracetam group

and low

medium and high-dose piracetam groups was significantly increased (

0.05)

whereas the level of MDA was reduced (

0.05). The expressions of Prdx6 and GSH-Px1 were significantly increased (

0.05，

0.01)

indicating that the SCL administration group was dose-dependent.

Conclusion

SCL can improve the learning and memory ability of

-gal-induced aging mice

which may be related to the anti-oxidation ability of SCL and the up-regulation of Prdx6 and GSH-Px1 expressions in mouse brain tissue.

关键词

Keywords

references

HUANG Y , MUCKE L . Alzheimer mechanisms and therapeutic strategies [J]. Cell , 2012 , 148 ( 6 ): 1204 - 1222 .

RAFFAELLA D M . Sensing the breaks: cytosolic chromatin in senescence and cancer [J]. Trends Mol Med , 2017 , 23 ( 12 ): 1067 - 1070 .

张玉串 . 补肾健脾调肝法对去势雌性大鼠ER及衰老因子的研究 [D]. 广州：广州中医药大学 , 2014 .

刘杰 , 徐剑 , 郭江涛 . 五味子活性成分及药理作用研究进展 [J]. 中国实验方剂学杂志 , 2019 , 25 ( 11 ): 206 - 215 .

QIU F , LIU H , DUAN H , et al . Isolation, structural elucidation of three new triterpenoids from the stems and leaves of Schisandra chinensis (Turcz) Baill [J]. Molecules , 2018 , 23 ( 7 ): 1624 - 1630 .

魏雪苗 , 侯建成 , 刘洋 , 等 . 五味子木脂素研究进展 [J]. 吉林医药学院学报 , 2018 , 39 ( 2 ): 115 - 118 .

SZOPA A , EKIERT R , EKIERT H . Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies [J]. Phytochem Rev , 2017 , 16 ( 2 ): 195 - 218 .

ZHANG R , WANG Y , ZHU D , et al . The protective effect of north schisandra lignans on vascular endothelial cell oxidation injuries [J]. Technol Health Care , 2016 , 29 ( s2 ): 651 - 657 .

姜恩平 , 王帅群 , 王卓 , 等．北五味子总木脂素对脑缺血模型大鼠神经细胞凋亡及p-Akt表达的影响 [J]. 中国中药杂志 , 2014 , 39 ( 9 ): 1680 - 1684 ．

刘宏 , 李贺 , 苑荣爽 , 等 . 北五味子总木脂素对C57BL/6小鼠高脂血症的影响 [J]. 食品科学 , 2016 , 37 ( 11 ): 218 - 221 .

于春艳 , 于春荣 , 李贺 , 等 . 北五味子总木脂素减轻内质网途径凋亡延缓小鼠脑衰老 [J]. 中国病理生理杂志 , 2014 , 30 ( 11 ): 1967 - 1973 .

BERNHARD J E , MCKENNA G W , HAMILTON D A , et al . Inhibiting Ras prenylation increases the radiosensitivity of human tumor cell lines with activating mutations of Ras oncogenes [J]. Cancer Res , 1998 , 58 ( 8 ): 1754 - 1761 .

原慧萍 , 杨泽 . 氧化应激与衰老研究进展 [J]. 中国老年保健医学 , 2015 , 13 ( 5 ): 14 - 17 .

HU D , YANG Z , YAO X , et al . Dibenzocyclooctadiene lignans from Schisandra chinensis and their inhibitory activity on NO production in lipopolysaccharide-activated microglia cells [J]． Phytochemistry , 2014 , doi: 10.1016/j.phytochem.2014.04.014 http://dx.doi.org/10.1016/j.phytochem.2014.04.014 .

CHEN L , YAO H , CHEN X , et al . Ginsenoside Rg 1 decreases oxidativestress and down-regulates Akt/mTOR signaling to attenuatecognitive impairment in mice and senescence of neural stemcells induced by D -galactose [J]. Neurochem Res , 2018 , doi: 10.1007/s11064-017-2438-y http://dx.doi.org/10.1007/s11064-017-2438-y .

WU S X , HAN X M , JIANG X W , et al . The effects of two different multivitamins on aging mice [J]. Chinese J Physiol , 2017 , 60 ( 5 ): 284 - 292 .

KOLTOVER V K . Free radical timer of aging：from chemistry of free radicals to systems theory of reliability [J]. Curr Aging Sci , 2017 , 10 ( 1 ): 12 - 17 .

KRISTINA F , FABIAN G , LINDA L , et al . Tyrosine substitution of a conserved active-site histidine residue activates plasmodium falciparum peroxiredoxin 6 [J]. Protein Sci , 2019 , 28 ( 1 ): 100 - 110 .

GUO J H , XING G L , FANG X H , et al . Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6 [J]. World J Gastroentero , 2017 , 23 ( 8 ): 1434 - 1442 .

YANG Y F , XIE F Y , QIN D D , et al . The orphan nuclear receptor NR4A1 attenuates oxidative stress-induced β cells apoptosis via up-regulation of glutathione peroxidase 1 [J]. Life Sci , 2018 , doi: 10.1016/j.lfs.2018.04.027 http://dx.doi.org/10.1016/j.lfs.2018.04.027 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

基于UPLC-Q-TOF-MS结合网络药理学探讨黑逍遥散改善失眠大鼠学习记忆能力的药效物质基础及作用机制

开心散对APP/PS1小鼠学习记忆能力和突触功能的机制

清心开窍方对老年痴呆小鼠脑自由基代谢及海马CA1区神经细胞形态的影响

益智饮对阿尔茨海默病大鼠学习记忆能力的影响及抗氧化作用