Deoxygedunin对D-半乳糖联合AlCl3诱导大鼠阿尔茨海默病病理性改变的影响

doi:10.12047/j.cjap.5732.2018.111

摘要/Abstract

摘要： 目的：观察Deoxygedunin对D-半乳糖联合AlCl₃诱导的阿尔茨海默病模型大鼠Aβ沉积、学习记忆和氧化应激的影响及其可能机制。方法：健康成年雄性SD大鼠随机分为3组（n=12）：对照组（Control）、模型组（AD）和干预组（AD+Deo）。Morris水迷宫实验检测大鼠学习记忆和认知功能；采用酶联免疫吸附法（ELISA）检测大鼠海马组织匀浆中谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）和丙二醛（MDA）含量；免疫组织化学检测大鼠大脑皮层tau蛋白表达情况；Western blot实验用于检测TrkB信号通路上ERK1、AKT和TrkB蛋白的表达。结果：水迷宫结果显示，与对照组相比，D-半乳糖联合AlCl₃诱导的大鼠逃避潜伏期显著增加（P<0.05）。Deoxygedunin可逆转模型组逃避潜伏期的增加（P<0.05）。在去除平台的第7日，与对照组和干预组相比，模型组大鼠表现出逃避潜伏期增加（P<0.01），穿越平台次数较少（P<0.05）；免疫组织化学和ELISA实验结果显示，与对照组相比，模型组Aβ、tau蛋白表达显著增加（P<0.01），SOD、GSH-Px活性显著降低，MDA含量明显升高。与模型组相比，Deoxygedunin可逆转模型组Aβ、tau蛋白表达的增多（P<0.01），SOD、GSH-Px活性显著降低（P<0.05），MDA含量明显升高（P<0.05）；Western blot结果显示，Deoxygedunin干预可逆转模型组海马TrkB、AKT和ERK1的磷酸化水平的降低。结论：Deoxygedunin可通过激活TrkB信号转导通路显著逆转Aβ沉积，氧化应激和认知缺陷，提示Deoxygedunin可能作为减轻D-半乳糖联合AlCl₃诱导AD样病理功能障碍潜在的治疗备选药物。

关键词: 阿尔茨海默病, Deoxygedunin, D-半乳糖, β淀粉样蛋白, Tau蛋白, 大鼠

Abstract: Objective: To investigate the effects of Deoxygedunin on Aβ deposition, learning memory, and oxidative stress induced by D-galactose combined with AlCl₃ in model rats with Alzheimer's disease and its possible mechanism.Methods: Male SD rats were randomly divided into three groups (n=12):control group, model group (AD) and intervention group (AD+Deo). Morris water maze test was used to detect learning/memory and cognitive function in rats.Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) contents in homogenate of hippocampus were detected by enzyme-linked immunosorbent assay (ELISA).Tau protein expression in rat cerebral cortex was detected by immunohistochemistry.Western blot was used to detect the expressions of extracellular signal regulated kinase 1(ERK1), protein kinase B (PKB) and tropomyosin-related kinase B (TrkB) on TrkB signaling pathway.Results: The results of water maze test showed that D-galactose combined with AlCl₃ induced a significant increase in the escape latency compared with the control group (P<0.05).Deoxygedunin could reverse the increase of the escape latency of the model group (P<0.05).On the 7th day after removal of the platform, the model group showed an increase in escape latency compared with the control group and the intervention group (P<0.01), and the number of crossing platforms was declined (P<0.05); The results of immunohistochemistry and ELISA showed that the expressions of Aβ and tau protein in the model group were increased significantly compared with those of the control group (P<0.01).The activities of SOD and GSH-Px were decreased significantly and the content of MDA was increased significantly.Compared with the model group, Deoxygedunin could reverse the increase of the expressions of Aβ and tau protein (P<0.01), the decrease of SOD and GSH-Px activities (P<0.05) and the increase of the MDA content (P<0.05).Western blot results showed that Deoxygedunin treatment reversed the decreased phosphorylation levels of TrkB, AKT and ERK1 in hippocampus of the model group.Conclusion: Supplement of Deoxygedunin can significantly reverse Aβ deposition, oxidative stress and cognitive deficits by activating the TrkB signal transduction pathway, which suggest that Deoxygedunin may serve as a promising therapeutic candidate for attenuating AD-like pathological dysfunction induced by D-galactose combined with AlCl₃.

Key words: Alzheimer's disease, deoxygedunin, D-galactose, amyloid β, Tau protein, rat

陈建国, 江祺川, 温博, 王若雅, 吴亚更, 李响. Deoxygedunin对D-半乳糖联合AlCl₃诱导大鼠阿尔茨海默病病理性改变的影响[J]. 中国应用生理学杂志, 2018, 34(6): 496-500.

CHEN Jian-guo, JIANG Qi-chuan, WEN Bo, WANG Ruo-ya, WU Ya-geng, LI Xiang. Effects of deoxygedunin on Alzheimer-like pathologic dysfunction induced by D-galactose combined with AlCl₃[J]. CJAP, 2018, 34(6): 496-500.

参考文献

[1] Ossenkoppele R, Pijnenburg YA, Perry DC, et al. The behavioural/dysexecutive variant of Alzheimer's disease:clinical, neuroimaging and pathological features[J]. Brain, 2015, 138(Pt 9):2732-2749.
[2] Ajith TA, Padmajanair G.Mitochondrial pharmaceutics:a new therapeutic strategy to ameliorate oxidative stress in Alzheimer's disease[J]. Curr Aging Sci, 2015, 8(3):235-240.
[3] Cheignon C, Tomas M, Bonnefont-Rousselot D, et al. Oxidative stress and the amyloid beta peptide in Alzheimer's disease[J]. Redox Biol, 2018, 14:450-464.
[4] Tramutola A, Lanzillotta C, Perluigi M, et al. Oxidative stress, protein modification and Alzheimer disease[J]. Brain Res Bull, 2017, 133:88-96.
[5] Coelho FG, Vital TM, Stein AM, et al. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease[J]. J Alzheimers Dis, 2014, 39(2):401-408.
[6] 董雪帆, 王婷, 李甜, 等. APPswe/PS1dE9转基因小鼠小脑内突触素及BDNF/Trk-B蛋白表达的变化[J]. 中国应用生理学杂志, 2017, 33(6):488-492.
[7] Nie S, Xu Y, Chen G, et al. Small molecule TrkB agonist deoxygedunin protects nigrostriatal dopaminergic neurons from 6-OHDA and MPTP induced neurotoxicity in rodents[J]. Neuropharmacology, 2015, 99:448-458.
[8] Hu Y, Ding WT, Zhu XN, et al. A mini review:Tau transgenic mouse models and olfactory dysfunction in Alzheimer's Disease[J]. Chin J Appl Physiol, 2015, 31(6):481-490.
[9] Lee JH, Jeong SK, Kim BC, et al. Donepezil across the spectrum of Alzheimer's disease:dose optimization and clinical relevance[J]. Acta Neurol Scand, 2015, 131(5):259-267.
[10] Wei Y, Liu D, Zheng Y, et al. Protective effects of kinetin against aluminum chloride and D-galactose induced cognitive impairment and oxidative damage in mouse[J]. Brain Res Bull, 2017, 134:262-272.
[11] Peng XM, Gao L, Huo SX, et al. The mechanism of memory enhancement of acteoside (verbascoside) in the senescent mouse model induced by a combination of D-gal and AlCl3[J]. Phytother Res, 2015, 29(8):1137-1144.
[12] Zhang F, Kang Z, Li W, et al. Roles of brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) signalling in Alzheimer's disease[J]. J Clin Neurosci, 2012, 19(7):946-949.
[13] 唐量, 亢依婷, 尹博, 等. 负重爬梯与有氧跑台运动对糖尿病大鼠学习记忆能力的影响及其机制探讨[J]. 中国应用生理学杂志, 2017, 33(5):436-440.
[14] Jang SW, Liu X, Chan CB, et al. Deoxygedunin, a natural product with potent neurotrophic activity in mice[J]. PLoS One, 2010, 5(7):e11528.
[15] Chiroma SM, Mohd Moklas MA, Mat Taib CN, et al. d-galactose and aluminium chloride induced rat model with cognitive impairments[J].Biomed Pharmacother, 2018, 103:1602-1608.
[16] English AW, Liu K, Nicolini JM, et al. Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves[J]. Proc Natl Acad Sci U S A, 2013, 110(40):16217-16222.
[17] Wang C, Zhang X, Teng Z, et al. Downregulation of PI3K/Akt/mTOR signaling pathway in curcumin-induced autophagy in APP/PS1 double transgenic mice[J]. Eur J Pharmacol, 2014, 740:312-320.
[18] 蒋方, 孙凤仙, 徐淑梅. β片层阻断肽H102对双转基因AD小鼠海马脑区APP代谢酶的影响[J]. 中国应用生理学杂志, 2017, 33(4):299-303.
[19] Noel A, Poitras I, Julien J, et al. ERK (MAPK) does not phosphorylate tau under physiological conditions in vivo or in vitro[J]. Neurobiol Aging, 2015, 36(2):901-902.

Deoxygedunin对D-半乳糖联合AlCl₃诱导大鼠阿尔茨海默病病理性改变的影响

Effects of deoxygedunin on Alzheimer-like pathologic dysfunction induced by D-galactose combined with AlCl₃

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	扈敬, 李法东, 邵小婷, 李思葳, 张欣颖, 赵冰冰, 徐长庆, 魏璨. 精胺对高糖引起的大鼠心肌纤维化的影响及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 193-196.
[2]	朱建忠, 赵灿, 隋月林, 刘媛媛, 乔跃兵. 瘦素对糖尿病大鼠糖脂代谢及炎性因子的影响[J]. 中国应用生理学杂志, 2020, 36(3): 197-201.
[3]	孙晓娟, 冯武龙, 侯娜, 李娜, 姜蔚丽. 有氧运动和白藜芦醇对2型糖尿病大鼠肾脏JAK2及TGF-β1的影响[J]. 中国应用生理学杂志, 2020, 36(3): 202-206.
[4]	石慧, 梁晓珊, 黄丽文, 罗之刚, 谭龙. 一种高尿酸血症大鼠模型诱导方法的改良和效果评价研究[J]. 中国应用生理学杂志, 2020, 36(3): 223-227.
[5]	杨琼, 潘娅, 陈粲, 戴桃李. 阿尼西坦对血管性痴呆大鼠的治疗作用[J]. 中国应用生理学杂志, 2020, 36(3): 232-234.
[6]	韩洁, 刘子怡, 方振, 田蕾, 杨丹凤, 袭著革, 刘晓华. 重复制动应激对雌性大鼠下丘脑-垂体-卵巢轴的影响[J]. 中国应用生理学杂志, 2020, 36(3): 245-249.
[7]	孙景然, 樊祢祢, 张桢, 吴瑾, 韩殿鹏, 白家磊, 杜连群, 房彦军. 有机磷阻燃剂TDCIPP对雌性大鼠甲状腺的潜在毒性作用[J]. 中国应用生理学杂志, 2020, 36(3): 250-254.
[8]	陈宇峰, 董凡赫, 楼云玮, 寿今豪, 张慧婷, 周一超, 严明, 毛红娇, 张云. 补骨脂素对TCP磨损颗粒所致大鼠成骨细胞损伤的干预作用及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 255-260.
[9]	李家卉, 张敏, 付子豪, 李勇枝, 王佳平, 高峰, 董玲. 经皮穿刺抽取大鼠脑脊液方法的改良[J]. 中国应用生理学杂志, 2020, 36(3): 265-267.
[10]	徐昌顺, 孙培, 林春. 改良型大鼠鞘内穿刺置管针及导管末端注药装置在大鼠鞘内置管术中的应用研究[J]. 中国应用生理学杂志, 2020, 36(3): 283-288.
[11]	王凌星, 洪姗燕, 杨美丽, 黄红红. 丁苯酞对睡眠剥夺大鼠额叶小胶质细胞活化的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 106-110.
[12]	完建永, 张勇, 刘世强, 华田苗, 孙庆艳. 运动对胰岛素抵抗大鼠肝脏BIM信号通路的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 115-118.
[13]	姚良雪, 韩家鑫, 魏培韵, 侯思博, 何潇剑, 张瑞岭, 杜爱林. 丁苯酞对慢性酒精中毒大鼠海马、杏仁核H₂S/CBS通路及学习记忆能力的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 138-142.
[14]	窦丽. 游泳训练对高血压大鼠血压及血栓前状态分子的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 161-164.
[15]	苏艳红, 袁乾坤, 肖蓉, 陈娟, 李强, 张世超. 抗阻训练对增龄大鼠骨骼肌线粒体功能的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 165-170.