天然产物研究与开发 ›› 2018, Vol. 30 ›› Issue (1): 89-96.doi: 10.16333/j.1001-6880.2018.1.016

• 开发研究 • 上一篇    下一篇

天麻素对Aβ1-42致痴呆大鼠模型的保护作用及机制探究

冯超1,姜霁芳2,唐美霞3,陈萌2*   

  1. 1烟台山医院;2 烟台毓璜顶医院;3滨州医学院中西医结合学院,烟台 264003
  • 出版日期:2018-01-26 发布日期:2018-01-30

Protective Effect of Gastrodin on a Rat Model of Amyloid-β1–42-Induced Alzheimer’s Disease

FENG Chao1,JIANG Ji-fang2,TANG Mei-xia3,CHEN Meng2*   

  1. 1Yantai Mountain Hospital; 2Laishan Branch,Yantai Yuhuangding Hospital; 3Binzhou Medical University,Yantai 264003,China  
  • Online:2018-01-26 Published:2018-01-30

摘要: 为了探讨天麻素(Gastrodin)对Aβ1-42致痴呆大鼠的药理作用及其作用机制,本研究主要通过向SD大鼠海马区微注射Aβ1-42建立大鼠痴呆模型,并在此模型的基础上评价天麻素对阿尔茨海默病的药理作用。实验分为5组:正常组、模型组、低剂量天麻素治疗组(1 mg/kg)、中剂量天麻素治疗组(5 mg/kg)和高剂量天麻素治疗组(25 mg/kg)。天麻素治疗组SD大鼠微注射Aβ1-42后,连续灌胃天麻素14 d,模型组SD大鼠微注射Aβ1-42后,连续灌胃生理盐水14 d。通过水迷宫实验检测各组大鼠行为学变化;用ELISA法检测脑组织中SOD活性、MDA含量和GSH-Px的含量。通过HE染色观察各组SD大鼠脑组织的病理学变化。通过TUNEL法检测各组大鼠脑组织的脑细胞凋亡情况。使用Western blot法检测脑组织中GSK-3β的磷酸化水平。结果发现,模型组大鼠的学习记忆能力明显下降,脑组织出现严重的损伤和凋亡现象,并且脑组织中SOD和GSH-Px的活性明显降低,而MDA含量显著升高。通过天麻素的治疗干预后,我们发现,天麻素治疗可以显著逆转上述的损伤现象,并且天麻素的这种保护作用具有一定的剂量依赖性。与此同时,我们还发现,高剂量天麻素可显著升高脑组织中GSK-3β磷酸化水平。以上结果表明,天麻素对海马区微注射Aβ1-42致痴呆SD大鼠有一定的改善和保护作用,其作用机制可能是激活GSK-3β信号通路发挥抗氧化和抗凋亡作用。

关键词: 天麻素;&beta, -淀粉样蛋白;阿尔茨海默病;抗氧化;抗凋亡;GSK-3&beta,

Abstract: The objective of the present study was to evaluate the modulating effects of gastrodin on cognitive deficits.Rats were administered bilaterally in hippocampal CA1 area by injecting Aβ1-42 to produce an animal model of Alzheimer’s Disease (AD).The rats were randomly subdivided into 5 groups:Control group,Model group,Gastrodin-L (1 mg/kg),Gastrodin-M (5 mg/kg) and Gastrodin-H (25 mg/kg).The Morris water maze and passive avoidance tests were used to determine the neuroprotective effects of gastrodin on Aβ1-42-induced learning and memory impairments.The levels of superoxide dismutase (SOD),malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were analyzed to determine the oxidative stress status by ELISA.Brain ultrastructure was observed via optical microscopy (HE staining).The apoptosis of neurons was detected by TUNEL staining,The proteins levels of total glycogen synthase kinase-3β (GSK-3β) and phospho-GSK-3β (p-GSK-3β) were measured by Western blot.The results showed that the memory function was significantly reduced in model group of rats,and severe brain injury and neuronal apoptosis were also observed in the model group.Compare with control group,the activities of total SOD and GSH-Px were markedly decreased,but the levels of MDA were significantly increased in the model group.Gastrodin (5 mg/kg and 25 mg/kg) improved previous learning and memory impairments than the model groups.Compared with the model group,the activities of total SOD and GSH-Px were markedly enhanced,but the levels of MDA was significantly reduced in Gastrodin-M and Gastrodin-H groups.Meanwhile,Gastrodin (5 mg/kg and 25 mg/kg) also significantly attenuated Aβ1-42-induced brain injury and neuronal apoptosis.In addition,the expression levels of p-GSK-3β expression was upregulated in the Gastrodin-H group.Taken together,our findings suggest that Gastrodin have beneficial effects on the cognitive impairments seen in an Aβ1-42-induced model of Alzheimer's disease via inhibiting oxidative stress and anti-apoptotic responses.

Key words: Gastrodin;Alzheimer disease, Aβ1-42, antioxidant, anti-apoptotic, GSK-3β

中图分类号: 

R965