北五味子酸性多糖对阿尔茨海默病模型小鼠学习记忆能力的改善作用

doi:10.13481/j.1671-587x.20170609

吉林大学学报(医学版) ›› 2017, Vol. 43 ›› Issue (06): 1115-1120.doi: 10.13481/j.1671-587x.20170609

北五味子酸性多糖对阿尔茨海默病模型小鼠学习记忆能力的改善作用

李贺¹, 刘聪¹, 李宁¹, 王春梅¹, 敬舒², 孙靖辉¹, 孙红霞¹, 张成义¹, 陈建光¹

1. 北华大学药学院药理学教研室, 吉林吉林 132013;
2. 北华大学附属医院普外科, 吉林吉林 132001

收稿日期:2017-06-05 出版日期:2017-11-28 发布日期:2017-12-01
通讯作者: 陈建光,教授,硕士研究生导师(Tel:0432-64608080,E-mail:chenjg@beihua.edu.cn) E-mail:chenjg@beihua.edu.cn
作者简介:李贺(1977-),女,副教授,吉林省四平市人,医学博士,主要从事神经药理学方面的研究。
基金资助:
吉林省科技厅科研项目资助课题（20150101230JC，201603103YY）；吉林省吉林市科技计划项目资助课题（20166018，20163054）

Improvement of acidic polysaccharose of Schisandra Chinensis on learning and memory functions of Alzheimer's disease model mice

LI He¹, LIU Cong¹, LI Ning¹, WANG Chunmei¹, JING Shu², SUN Jinghui¹, SUN Hongxia¹, ZHANG Chengyi¹, CHEN Jianguang¹

1. Department of Pharmacology, College of Pharmacy, Beihua University, Jilin 132013, China;
2. Department of General Surgery, Affiliated Hospital, Beihua University, Jilin 132001, China

Received:2017-06-05 Online:2017-11-28 Published:2017-12-01

摘要/Abstract

摘要： 目的：观察北五味子酸性多糖（SCP-A）对Aβ_25-35致阿尔茨海默病（AD）模型小鼠学习记忆能力的改善作用，并阐明其相关机制。方法：75只雄性C57BL小鼠随机分为空白组（侧脑室注射生理盐水，灌胃蒸馏水），模型组（侧脑室注射Aβ_25-35，灌胃蒸馏水），5、10和20 mg·kg^-1 SCP-A组（侧脑室注射Aβ_25-35，灌胃SCP-A），每组15只。灌胃药物每日1次，连续14 d，于第8天给予Aβ_25-35进行侧脑室注射。给药完毕后，第15天依次进行避暗实验及Morris水迷宫实验观察小鼠的潜伏期、错误次数、找到平台时间、穿越平台次数和目标象限停留时间，Western blotting法检测小鼠海马组织中Tau蛋白、糖原合成酶激酶3（GSK-3β）及其磷酸化蛋白的表达水平。结果：避暗实验，与空白组比较，模型组小鼠潜伏期明显缩短，错误次数明显升高（P<0.01）；与模型组比较，10和20 mg·kg^-1 SCP-A组小鼠潜伏期明显延长（P<0.01），错误次数明显减少（P<0.05或P<0.01）。Morris水迷宫，与空白组比较，模型组小鼠找到平台时间明显延长（P<0.01），穿越平台次数及目标象限停留时间明显缩短（P<0.01）；与模型组比较，10和20 mg·kg^-1 SCP-A组小鼠找到平台时间明显缩短（P<0.01），穿过平台次数及平台区域停留时间明显增加（P<0.01）。Western blotting法检测，与模型组比较，20 mg·kg^-1SCP-A组小鼠海马组织中磷酸化蛋白Tau Ser199、Tau Ser396及Tau Ser404表达水平明显降低（P<0.05），GSK-3β表达水平明显降低（P<0.01），磷酸化蛋白GSK-3β Tyr216相对表达水平明显降低（P<0.05），磷酸化蛋白GSK-3β Ser9相对表达水平明显升高（P<0.05）。结论：SCP-A具有抗AD作用，该作用与其调节GSK-3β活性进而降低海马组织中Tau蛋白磷酸化水平有关。

关键词: 北五味子, 酸性多糖, 阿尔茨海默病, Tau蛋白, 糖原合成酶激酶3

Abstract: Objective:To observe the improvement of acidic polysaccharose of Schisandrae Chinensis (SCP-A) on the learning and memory functions of Alzheimer's disease (AD) model mice induced by Aβ_25-35, and to clarify the related mechanisms. Methods:A total of 75 male C57BL mice were randomly divided into control group (injected with saline in intracerebroventricular, given distilled water intragastrically), model group (injected with Aβ_25-35 intracerebroventricularly, given distilled water intragastrically), and 5, 10,20 mg·kg^-1 SCP-A groups (injected with Aβ_25-35 intracerebroventricularly, given SCP-A intragastrically)(n=15). The agents were administered once daily for 14 d, in which Aβ_25-35 was injected intracerebroventricularly on the 8th day. On the 15th day after administration, step-through test and Morris water maze test were used to detect the escape latency, number of errors,and time of finding platform, number of passing platforms,dwell time in target quadrant of the mice; Western blotting method was used to detected the levels of Tau,GSK-3β and their phosphorylated proteins in hippocampus tissue of the mice. Results:The step-through test results showed that compared with control group,the escape latency of the mice in model group was obviously shortened and the number of errors was significantly increased(P<0.01); compared with model group, the escape latencies of the mice in 10 and 20 mg·kg^-1 SCP-A groups were significantly prolonged (P<0.01), the number of errors was significantly decreased (P<0.05 or P<0.01). The Morris water maze test results showed that compared with control group, the time of finding platform of the mice in model group was significantly prolonged,the number of passing platform and dwell time in target quadrant were significantly reduced(P<0.01); compared with model group, the time of finding platform of the mice in 10 and 20 mg·kg^-1 SCP-A groups was significantly shortened(P<0.01),and the number of passing platform and the dwell time in target quadrant were significantly increased (P<0.01). The Western blotting results showed that compared with model group, the expression levels of phosphorylated protein Tau Ser199, Tau Ser396 and Tau Ser404 in hippocampus of the mice in 20 mg·kg^-1 SCP-A group were significantly decreased(P<0.05), and the expression level of GSK-3β was significantly decreased(P<0.01); the expression level of phosphorylated protein GSK-3β Tyr216 was significantly decreased, and the expression level of phosphorylated protein GSK-3β Ser9 was significantly increased (P<0.05). Conclusion:SCP-A has an anti-AD effect, which is related to regulating the activity of GSK-3β to reduce the level of phosphorylated protein Tau in the hippocampus tissue of the mice.

Key words: Alzheimer's disease, Tau, GSK-3β, Schisandra chinensis, acidic polysaccharides

中图分类号:

R285

李贺, 刘聪, 李宁, 王春梅, 敬舒, 孙靖辉, 孙红霞, 张成义, 陈建光. 北五味子酸性多糖对阿尔茨海默病模型小鼠学习记忆能力的改善作用[J]. 吉林大学学报(医学版), 2017, 43(06): 1115-1120.

LI He, LIU Cong, LI Ning, WANG Chunmei, JING Shu, SUN Jinghui, SUN Hongxia, ZHANG Chengyi, CHEN Jianguang. Improvement of acidic polysaccharose of Schisandra Chinensis on learning and memory functions of Alzheimer's disease model mice[J]. Journal of Jilin University Medicine Edition, 2017, 43(06): 1115-1120.

参考文献

[1] 白娟.吡格列酮对AD大鼠模型学习记忆及GSK-3β、p-tau蛋白的影响[D].太原:山西医科大学,2011.
[2] Wang HY, Lee DH, D'Andrea MR, et al.beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity.Implications for Alzheimer's disease pathology[J].J Biol Chem,2000,275(8):5626-5632.
[3] 汪琴. 自主运动影响Aβ_25-35对C57/bl6小鼠的神经毒性作用及其机制[D].南京:南京医科大学,2014.
[4] 李宁,刘聪,李佳鸿,等.五味子淫羊藿混合提取物对东莨菪碱致小鼠学习记忆障碍的改善作用[J]. 吉林大学学报:医学版,2017,43(1):42-46.
[5] 黄清松,李红枝,郑敏,等. 姬松茸粗多糖提高脑老化小鼠学习记忆能力的作用及其机制[J]. 吉林大学学报:医学版,2014,40(1):70-73.
[6] Mozayan M, Lee TJ. Statins prevent cholinesterase inhibitor blockade of sympathetic alpha7-n ACh R-mediated currents in rat superior cervical ganglion neurons[J]. Am J PhysiolHeart Circ Physiol,2007,293(3):1737-1744.
[7] Lee AY, Hwang BR, Lee MH, etal. Perilla frutescens var. japonica and rosmarinic acid improve amyloid-β_25-35 induced impairment of cognition and memory function.[J].Nutr Res Pract, 2016, 10(3):274-281.
[8] 刘港,胡增峣,杨胜,等. BALB/c和昆明小鼠Aβ侧脑室注射建立阿尔茨海默病小鼠模型比较[J]. 军事医学科学院院刊,2009,33(6):554-557.
[9] 吴婷,汪琴,孙建国,等.自主性运动对β淀粉样蛋白_(25-35)诱导小鼠神经细胞凋亡及氧化应激水平的影响[J]. 中国临床神经科学,2013,21(4):365-370.
[10] 李纪彤,齐越,姜鸿,等.温郁金水提物对Aβ_(25-35)致阿尔兹海默病小鼠模型行为学的影响[J].辽宁中医杂志,2017,44(3):633-636.
[11] 肖弯,曹晓璐,张容,等.黄芩苷改善Aβ_(25-35)诱导的小鼠学习和记忆障碍及可能机制[J]. 中国药理学与毒理学杂志,2017,31(1):59-64.
[12] 杨遥. REM睡眠剥夺对小鼠海马tau蛋白磷酸化的影响[D].石河子:石河子大学,2013.
[13] Liu SJ, Zhang AH, Li HL, et al. Overactivation of glycogen synthase kinase-3 by inhibition of phosphoinositol-3 kinase and protein kinase C leads to hyperphosphorylation of tau and impairment of spatial memory[J].J Neurochem, 2003, 87(6):1333-1344.
[14] Li XH, Lv BL, Xie JZ, et al. AGEs induce Alzheimer-like tau pathology and memory deficit via RAGE-mediated GSK-3 activation[J]. Neurobiol Aging, 2012, 33(7):1400-1410.
[15] Liu ZC, Fu ZQ, Song J, et al. Bip enhanced the association of GSK-3β with tau during ER stress both in vivo and in vitro[J]. J Alzheimers Dis, 2012, 29(4):727-740.
[16] Cho JH, Johnson GV. Glycogen synthase kinase 3β induces caspasecleaved tau aggregation in situ[J]. J Biol Chem, 2004, 279(52):54716-54723.

北五味子酸性多糖对阿尔茨海默病模型小鼠学习记忆能力的改善作用

Improvement of acidic polysaccharose of Schisandra Chinensis on learning and memory functions of Alzheimer's disease model mice

RichHTML

PDF (PC)

赞

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	李军, 姚静, 王国芳, 辛勤, 崔立坤, 齐汝霞. IL-33对阿尔茨海默病模型大鼠脑组织内β-淀粉样蛋白的清除作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(05): 908-913.
[2]	冯安琪, 刘楠, 朴美花, 苑野, 裴爱月, 刘娅, 冯春生. 异氟醚对缺锌APP/PS1转基因阿尔茨海默病模型小鼠海马神经元凋亡的影响[J]. 吉林大学学报(医学版), 2018, 44(01): 24-29.
[3]	苑荣爽, 李贺, 孙靖辉, 庄文越, 陈建光, 王春梅. 北五味子多糖对高脂诱导非酒精性脂肪性肝病大鼠的降血脂作用及其抗氧化活性[J]. 吉林大学学报(医学版), 2017, 43(06): 1103-1108.
[4]	孙晓红, 李嘉仪, 李洪涛, 谢宇, 孙新, 孔繁利. 北五味子多糖对脂多糖诱导中性粒细胞炎症的抑制作用[J]. 吉林大学学报(医学版), 2017, 43(05): 928-931.
[5]	陆国秀, 张国旭, 郝珊瑚, 郭佳, 张文文, 张景华, 王治国. 不同体质量指数阿尔茨海默病患者PET/CT联合显像和IL-6水平及ApoE表达率检测及其临床意义[J]. 吉林大学学报(医学版), 2017, 43(03): 611-614.
[6]	刘楠, 冯春生, 朴美花, 刘明, 孙宇田. 异氟醚对转APP基因小鼠脑内海马神经元蛋白质损伤和蛋白聚集的影响[J]. 吉林大学学报(医学版), 2016, 42(04): 665-670.
[7]	徐姗姗, 朴美花, 王艳姝, 刘楠, 裴爱月, 冯春生. 异氟醚对Aβ25-35诱导大鼠PC12细胞氧化应激损伤的影响及海藻糖的保护作用[J]. 吉林大学学报(医学版), 2015, 41(02): 207-212.
[8]	. 北五味子总木脂素对D-半乳糖诱导的小鼠脑衰老自噬和凋亡的影响[J]. 吉林大学学报(医学版), 2014, 40(06): 1210-1215.
[9]	邹泳国，周春燕，朴美花，刘楠，岳云，冯春生. 异氟醚对β淀粉样蛋白诱导的大鼠PC12细胞凋亡和内质网应激的影响及其机制[J]. 吉林大学学报(医学版), 2014, 40(02): 224-228.
[10]	李宜轩，陈建光，李凤，曲绍春，于晓风，睢大筼. 北五味子提取物对实验性肝纤维化大鼠肝损伤的保护作用[J]. 吉林大学学报(医学版), 2014, 40(02): 285-288.
[11]	王伟，朴美花，王艳姝，刘楠，岳云，冯春生. 异氟醚对Aβ25-35诱导大鼠PC12细胞自噬和凋亡的影响[J]. 吉林大学学报(医学版), 2014, 40(01): 49-54.
[12]	陈宝芝，李生，吴金滢，李贺，高晓旭，陈建光，王春梅. 北五味子粗多糖对四氯化碳致小鼠急性肝损伤的保护作用及其机制[J]. 吉林大学学报(医学版), 2014, 40(01): 92-96.
[13]	姚燕\|张天一,2,杨芳\|郭蔚莹\|张晴晴\|于雅琴. 罗格列酮对阿尔茨海默病治疗作用的Meta分析[J]. J4, 2012, 38(2): 296-302.
[14]	姜恩平, 吴金义, 陈建光. 北五味子总木脂素对H₂O₂诱导PC12细胞凋亡的影响[J]. J4, 2009, 35(3): 466-469.
[15]	孙潇，姜恩平，陈建光. 北五味子总木脂素对高脂血症大鼠心肌缺血再灌注损伤的保护作用及其机制[J]. J4, 2009, 35(2): 276-279.