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中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (6): 496-500.doi: 10.12047/j.cjap.5732.2018.111

• 研究论文 • 上一篇    下一篇

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

陈建国, 江祺川, 温博, 王若雅, 吴亚更, 李响   

  1. 锦州医科大学附属第一医院头颈外科, 辽宁 锦州 121001
  • 收稿日期:2018-08-03 修回日期:2018-11-05 出版日期:2018-11-28 发布日期:2019-03-09
  • 通讯作者: 陈建国 E-mail:cjg810958@163.com
  • 基金资助:
    辽宁省自然科学基金项目(201602272)

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

CHEN Jian-guo, JIANG Qi-chuan, WEN Bo, WANG Ruo-ya, WU Ya-geng, LI Xiang   

  1. Head and Neck Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China
  • Received:2018-08-03 Revised:2018-11-05 Online:2018-11-28 Published:2019-03-09
  • Supported by:
    辽宁省自然科学基金项目(201602272)

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

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