[1]谌 勤,罗洪斌,等.板桥党参通过PP2A信号通路改善AD模型大鼠认知功能障碍[J].中国药理学通报,2019,(09):1232-1239.[doi:10.3969/j.issn.1001-1978.2019.09.010]
 CHEN Qin,LUO Hong-bin,XIE Wen-zhi.Banqiao Codonopisis Pilosula improves cognitive dysfunction in AD model rats by PP2A signaling pathway[J].Chinese Pharmacological Bulletin,2019,(09):1232-1239.[doi:10.3969/j.issn.1001-1978.2019.09.010]
点击复制

板桥党参通过PP2A信号通路改善AD模型大鼠认知功能障碍()
分享到:

《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年09期
页码:
1232-1239
栏目:
论著
出版日期:
2019-09-09

文章信息/Info

Title:
Banqiao Codonopisis Pilosula improves cognitive dysfunction in AD model rats by PP2A signaling pathway
文章编号:
1001-1978(2019)09-1232-08
作者:
谌 勤1罗洪斌1 2 3谢文执1
湖北民族大学1.医学部生物化学与分子生物学教研室、2.科技学院生物化学与分子生物学教研室、3.神经精神共患病研究所,湖北 恩施 445000
Author(s):
CHEN Qin1 LUO Hong-bin123 XIE Wen-zhi1
1.Dept of Biochemistry and Molecular Biology, Medical College; 2.Dept of Biochemistry and Molecular Biology,Science and Technology College; 3.Institute of Neurological and Psychiatric Comorbidity, Hubei University for Nationalities, Enshi Hubei 445000, China
关键词:
阿尔茨海默病 板桥党参 PP2A Tau磷酸化 尼氏染色 认知功能
Keywords:
Alzheimer's disease Banqiao Codonopisis Pilosula PP2A Tau phosphorylation Nissl's staining cognitive function
分类号:
R-332; R282.71; R322.81; R338.64; R745.7; R977.6
DOI:
10.3969/j.issn.1001-1978.2019.09.010
文献标志码:
A
摘要:
目的 探讨板桥党参(BCP)对冈田酸(OA)诱导的阿尔茨海默病(AD)大鼠认知功能的保护作用及其可能机制。方法 将SD大鼠随机分为DMSO组﹑OA组﹑BCP低、中、高治疗组,每组分1周和2周组灌胃。水迷宫训练5 d,训练结束24 h后造模,DMSO组大鼠双侧脑海马各注射10% DMSO 1.5 μL,OA组和BCP治疗组同位置注射OA(0.392 mmol·L-1)1.5 μL。造模后,水迷宫测试观察大鼠空间学习能力; Western blot检测各组海马PP2A活性、Tau蛋白磷酸化水平及突触蛋白表达情况; 尼氏染色观察大鼠海马CA1﹑CA3区尼氏小体变化情况。结果 水迷宫实验发现,BCP能改善AD大鼠空间记忆障碍; Western blot结果显示,BCP能提高PP2A活性,增加突触蛋白表达量,同时减少Tau蛋白磷酸化水平。尼氏染色提示,BCP治疗组尼氏小体数量增加。结论 BCP能上调PP2A活性,降低Tau蛋白的磷酸化水平,同时提高突触相关蛋白表达水平,修复受损神经元。
Abstract:
Aim To investigate the protective effect of Banqiao Codonopsis pilosula(BCP)on cognitive function in rats with Alzheimer's disease(AD)induced by Okadaic acid(OA)and its possible mechanism.Methods SD rats were randomly divided into DMSO group, OA group and BCP low, medium, high treatment group.The rats were gavage administered in groups of one week and two weeks.The water maze training was continued for five days before modeling, and modeling was started 24 hours after the training.The bilateral hippocampus of DMSO group was injected with 10% DMSO 1.5 μL.OA group and BCP treatment group were injected with OA(0.392 mmol·L-1)1.5 μL.The water maze test was used to observe the spatial learning ability of rats.Western blot was used to observe the activity of PP2A, the phosphorylation of Tau protein and the expression of synaptic protein in hippocampus, and the Nissl's staining to observe the changes of Nissl bodies in hippocampus CA1 and CA3.Results Water maze experiments showed that BCP could improve spatial memory impairment in AD rats.Western blot results showed that BCP increased PP2A activity, increased synaptic protein expression, and decreased Tau protein phosphorylation.Nissl's staining suggested an increase in the number of Nissl bodies in BCP treatment group.Conclusions BCP can up-regulate PP2A activity, decrease the phosphorylation level of Tau protein, increase the expression of synaptic proteins, and repair damaged neurons.

参考文献/References:

[1] Hane F T, Lee B Y, Leonenko Z.Recent progress in Alzheimer's disease research, Part 1: pathology[J].J Alzheimers Dis, 2017, 57(1): 1-28.
[2] Kanae A, Akiko M O, Yosuke O, et al.Stabilization of microtubule-unbound Tau via Tau phosphorylation at Ser262/356 by Par-1/MARK contributes to augmentation of AD-related phosphorylation and Aβ42-induced Tau toxicity[J].PLOS Genet, 2016, 12(3): e1005917.
[3] Mahmoud B M, Youssra A H, Louise S.Nuclear Tau and its potential role in Alzheimer's disease[J].Biomolecules, 2016, 6(1): 9.
[4] Rudrabhatla P, Pant H C.Role of protein phosphatase 2A in Alzheimer's disease[J].Curr Alzheimer Res, 2011, 8(6): 623-32.
[5] Liu F, Grundke-Iqbal I, Iqbal K, et al.Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation[J].Eur J Neurosci, 2005, 22(8): 1942-50.
[6] Kamat P K, Rai S, Nath C.Okadaic acid induced neurotoxicity: an emerging tool to study Alzheimer's disease pathology[J].Neurotoxicology, 2013, 37(7): 163-72.
[7] 朱永红,吕 盼,欧晓群.板桥党参的研究现状[J].亚太传统医药,2012,8(3):189-90.
[7] Zhu Y H, Lyu P, Ou X Q.Research status of Banqiao Codonopisis Pilosula[J].Asia-Pac Tradit Med, 2012, 8(3): 189-90.
[8] 钟 灵,王振富,杨付明.板党多糖的抗衰老作用及机制[J].中国老年学杂志,2016,36(7):1554-6.
[8] Zhong L, Wang Z F, Yang F M.Anti-aging effect and mechanism of Banqiao Codonopsis pilosula polysaccharide[J].Chin J Gerontol, 2016, 36(7): 1554-6.
[9] 田先翔,赵晓芳,吴 勇,等.板党多糖对溃疡性结肠炎大鼠的防治作用及其分子机制研究[J].中国实验方剂学杂志,2016,22(10):107-12.
[9] Tian X X,Zhao X F,Wu Y, et al.Preventive and therapeutic effect of Banqiao Codonopsis Radix polysaccharide against ulcerative colitis in rats[J].Chin J Exp Tradi Med Form, 2016, 22(10): 107-12.
[10] 罗洪斌,刘翔宇,牟南樵,等.板桥党参对激活GSK-3β诱导的AD模型大鼠认知功能障碍的保护作用及其机制[J].中国药理学通报,2017,33(8):1060-7.
[10] Luo H B, Liu X Y, Mou N Q.Banqiao Codonopisis Pilosula improving cognitive dysfunction induced by high GSK-3β activity and its possible mechanism[J].Chin Pharmacol Bull, 2017, 33(8): 1060-7.
[11] 黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算[J].中国临床药理学与治疗学,2004,9(9):113-6.
[11] Huang J H, Huang X H, Chen Z Y, et al.Dose conversion among different animals and healthy volunteers in pharmacological study[J].Chin J Clin Pharmacol Ther, 2004, 9(9): 113-6.
[12] 姜 霞.L-肉毒碱在Alzheimer样Tau蛋白过度磷酸化和空间记忆障碍中的保护作用[D].武汉:华中科技大学,2008.
[12] Jiang X.Effect of L-Carnitine on Alzheimer-like tau hyperphosphorylation and spatial memory retention deficits[D].Wuhan: Huazhong University of Science and Technology, 2008.
[13] 谢文执,罗洪斌,谢枫枫,等.头顶一颗珠水煎液对阿尔茨海默病模型大鼠认知功能障碍的保护作用[J].中国药理学通报,2018,34(9):1268-75.
[13] Xie W Z, Luo H B, Xie F F.Trillium Tschonoskii Maxim improves cognitive dysfunction in Alzheimer's disease induced by okadaic acid in rat and its possible mechanism[J].Chin Pharmacol Bull, 2018, 34(9): 1268-75.
[14] 李雪莲,杨翠翠,张 兰.蛋白磷酸酶2A活性调节机制及其在阿尔茨海默病中的作用[J].国际药学研究杂志,2016,43(1):39-43.
[14] Li X L, Yang C C, Zhang L.Activity regulation mechanisms of protein phosphatase 2A and its role in Alzheimer's disease[J].J Int Pharm Res, 2016, 43(1): 39-43.
[15] Wang J Z, Liu F.Microtubule-associated protein Tau in development, degeneration and protection of neurons[J].Prog Neurobiol, 2008, 85(2): 148-75.
[16] 凯斯纳,马丁内斯(美).学习与记忆的神经生物学(第二版)[M].北京:科学出版社,2008,167.
[16] Kesner R P, Martinez J L.Neurobiology of Learning and Memory(Second Edition)[M].Beijing: Science Press of China, 2008, 167.

相似文献/References:

[1]冯利杰,张 瑾,丁 倩,等.自噬参与神经细胞中过表达tau和异常磷酸化tau蛋白的降解[J].中国药理学通报,2015,(03):356.[doi:10.3969/j.issn.1001-1978.2015.03.013]
 FENG Li-jie,ZHANG Jin,DING Qian,et al.Autophagy involved in overexpressed tau and okadaic acid-induced hyperphosphorylated tau degradation[J].Chinese Pharmacological Bulletin,2015,(09):356.[doi:10.3969/j.issn.1001-1978.2015.03.013]
[2]张 喻,肇玉明,王晓良,等.干细胞治疗阿尔茨海默病的研究进展及挑战[J].中国药理学通报,2015,(07):889.[doi:10.3969/j.issn.1001-1978.2015.07.001]
 ZHANG Yu,ZHAO Yu-ming,WANG Xiao-liang,et al.Advance and challenges in stem cell therapy for Alzheimer's disease[J].Chinese Pharmacological Bulletin,2015,(09):889.[doi:10.3969/j.issn.1001-1978.2015.07.001]
[3]李少恒,教亚男,姚璎珈,等.蛇床子素对感染APP基因的神经元突触的保护作用[J].中国药理学通报,2015,(10):1383.[doi:10.3969/j.issn.1001-1978.2015.10.012]
 LI Shao heng,JIAO Ya nan,YAO Ying jia,et al.Neuroprotective effect of osthole on neuron synapses infected APP gene[J].Chinese Pharmacological Bulletin,2015,(09):1383.[doi:10.3969/j.issn.1001-1978.2015.10.012]
[4]姚璎珈,孔 亮,教亚男,等.蛇床子素通过Wnt/β-catenin信号通路促进转染APP基因的神经干细胞分化为更多神经元且减少神经元凋亡[J].中国药理学通报,2015,(11):1516.[doi:10.3969/j.issn.1001-1978.2015.11.009]
 YAO Ying-jia,KONG Liang,JIAO Ya-nan,et al.Osthole promotes differentiation into neurons and reduces neuronal apoptosis via Wnt/β-catenin signaling pathway in APP transduced neural stem cells[J].Chinese Pharmacological Bulletin,2015,(09):1516.[doi:10.3969/j.issn.1001-1978.2015.11.009]
[5]李 琳,王晓良,彭 英.抗阿尔茨海默病天然产物及其药理学研究进展[J].中国药理学通报,2016,(02):159.[doi:10.3969/j.issn.1001-1978.2016.02.001]
 LI Lin,WANG Xiao-liang,PENG Ying.Pharmacological research of natural productsin the treatment of Alzheimer's disease[J].Chinese Pharmacological Bulletin,2016,(09):159.[doi:10.3969/j.issn.1001-1978.2016.02.001]
[6]赵静宇,汪梦霞,赵自明,等.基于Nrf2信号通路的三七总皂苷对Aβ25-35诱导PC12细胞凋亡的保护作用机制研究[J].中国药理学通报,2016,(03):343.[doi:10.3969/j.issn.1001-1978.2016.03.010]
 ZHAO Jing-yu,WANG Meng-xia,ZHAO Zi-ming,et al.Protective effect of Panax Notoginseng Saponins of Nrf2 signaling pathway on apoptosis of PC12 cells induced by Aβ25-35[J].Chinese Pharmacological Bulletin,2016,(09):343.[doi:10.3969/j.issn.1001-1978.2016.03.010]
[7]张兆旭,王德生.复智散通过细胞周期依赖性蛋白激酶5通路减轻皮层神经元Tau蛋白过度磷酸化[J].中国药理学通报,2016,(03):422.[doi:10.3969/j.issn.1001-1978.2016.03.024]
 ZHANG Zhao-xu,WANG De-sheng.Role of Fuzhisan in reducing Tau protein hyperphosphorylation in cortical neurons through a cyclin-dependent kinase 5 pathway[J].Chinese Pharmacological Bulletin,2016,(09):422.[doi:10.3969/j.issn.1001-1978.2016.03.024]
[8]董世芬,张胜威,孙建宁.沉默信息调节因子2同源蛋白1(SIRT1)与阿尔茨海默病研究进展[J].中国药理学通报,2016,(08):1041.[doi:10.3969/j.issn.1001-1978.2016.08.002]
 DONG Shi-fen,ZHANG Sheng-wei,SUN Jian-ning.Silent mating-type information regulator 2 homolog 1 (SIRT1)in Alzheimer's disease:an update on potential mechanisms[J].Chinese Pharmacological Bulletin,2016,(09):1041.[doi:10.3969/j.issn.1001-1978.2016.08.002]
[9]付文君,代 渊,魏江平,等.基于转基因细胞模型研究通络醒脑泡腾片对Aβ代谢的影响[J].中国药理学通报,2016,(11):1571.[doi:10.3969/j.issn.1001-1978.2016.11.018]
 FU Wen-jun,DAI Yuan,WEI Jiang-ping,et al.Effects of Tongluoxingnao effervescent tablet onAβ metabolism in transgenic cell model[J].Chinese Pharmacological Bulletin,2016,(09):1571.[doi:10.3969/j.issn.1001-1978.2016.11.018]
[10]韦 云,刘美霞,梁晓东,等.还脑益聪方提取物含药血清对APP/PS1双基因转染细胞γ分泌酶活性及相关蛋白表达的影响[J].中国药理学通报,2017,(03):417.[doi:10.3969/j.issn.1001-1978.2017.03.024]
 WEI Yun,LIU Mei-xia,LIANG Xiao-dong,et al.Effect of Huannao Yicong Decoction extract on activity of γ secretase and γ secretase-related regulation pathway of human APP/PS1 double transgenic cell line[J].Chinese Pharmacological Bulletin,2017,(09):417.[doi:10.3969/j.issn.1001-1978.2017.03.024]

备注/Memo

备注/Memo:
收稿日期:2019-04-11,修回日期:2019-06-20
基金项目:国家自然科学基金资助项目(No 81260172,81660223); 湖北省自然科学基金面上项目(No 2017CFB451); 湖北民族大学博士基金启动项目(No MY2012B015)
作者简介:谌 勤(1991-),女,硕士生,研究方向:传统医药学对神经退行性疾病的防治,E-mail:chenqin6824@sina.com;
罗洪斌(1968-),男,博士,副教授,硕士生导师,研究方向:神经退行性疾病的发病机制,通讯作者,E-mail: luohongbin6809@126.com
更新日期/Last Update: 2019-08-14