天然产物研究与开发 ›› 2021, Vol. 33 ›› Issue (1): 89-96.doi: 10.16333/j.1001-6880.2021.1.012

• 开发研究 • 上一篇    下一篇

阿里红多糖通过激活Nrf2/ARE通路改善阿尔茨海默病大鼠海马及脑皮层的氧化应激损伤

苏丽燕·赛力木江,依木然·马瑞士,丛媛媛,阿依江·哈拜克,帕丽达·阿不力孜*   

  1. 新疆医科大学药学院,乌鲁木齐 830011
  • 出版日期:2021-01-28 发布日期:2021-01-28
  • 基金资助:
    国家自然科学基金(81760755);新疆维吾尔自治区自然科学基金联合基金(2019D01C216);新疆维吾尔自治区高校科研计划自然科学项目(XJEDU2020Y025)

Effect of Fomes officinalis Ames polysaccharides on Nrf2/ARE signal pathway in AD rat model induced by Aβ1-42

SULIYAN Sai-li-mu-jiang,YIMURAN Ma-rui-shi,CONG Yuan-yuan,AYIJIANG Ha-bai-ke,PALIDA A-bu-li-zi*#br#

#br#
  

  1. College of Pharmacy,Xinjiang Medical University,Urumqi 830011,China
  • Online:2021-01-28 Published:2021-01-28

摘要:

探讨阿里红多糖(Fomes officinalis Ames polysaccharides,FOPS)抗氧化应激的作用,并从Nrf2/ARE信号通路研究其作用机制。72只健康雄性SD大鼠称体质量并按随机原则分为空白组、模型组、盐酸多奈哌齐组(0.5 mg/kg)、阿里红多糖高、中、低剂量组(100、50、25 mg/kg),每组12只。采用大鼠双侧海马CA1区注射(5 μL/侧)Aβ1-42建立AD大鼠模型,给药30天,Morris水迷宫检测行为学变化,荧光定量RT-qPCR和蛋白免疫印迹法(Western blotting)检测各组大鼠脑皮层和海马组织中结构蛋白Keap1、Nrf2及下游抗氧化蛋白HO-1、NQO1 mRNA及蛋白含量。结果发现,干预30天后,与空白组比较,AD模型组大鼠学习记忆能力显著下降(P<0.01),大鼠海马区及脑皮层Nrf2、NQO1、HO-1的mRNA含量及蛋白表达量显著下降(P<0.01),而Keap1 mRNA含量及蛋白表达量显著升高(P<0.01);与模型组比较,盐酸多奈哌齐和阿里红多糖高、中剂量组大鼠的学习记忆能力显著升高(P<0.01),大鼠海马区及脑皮层Nrf2、NQO1、HO-1 mRNA含量及蛋白表达量显著升高(P<0.05,P<0.01),Keap1 mRNA含量及蛋白表达量显著降低(P<0.05,P<0.01)。研究表明阿里红多糖通过调节Keap1的表达,促进Nrf2激活,诱导NQO1、HO-1的表达,发挥提高机体抗氧化损伤作用,从而改善AD大鼠学习记忆能力。

关键词: 阿里红多糖, 氧化应激, Nrf2/ARE, 脑皮质层, 海马组织

Abstract:

To explore the effect of Fomes officinalis Ames polysaccharides (FOPS) on anti-oxidative stress,and study its mechanism from the Nrf2/ARE signaling pathway.Seventy two eligible male SD rats were weighed and divided into sham control group,AD model group,donepezil hydrochloride group (0.5 mg/kg),FOPS high,medium and low dose groups (100,50,25 mg/kg),with 12 rats in each group.The AD rat model was established by injecting (5 μL/side) Aβ1-42 in the hippocampal CA1 area of both sides of the rat.After 30 days of treatment,The learning and memory ability was tested by Morris water maze.RT-qPCR and Western blotting were used to detect the structural proteins Keap1,Nrf2 and the downstream antioxidant protein HO-1,NQO1 mRNA and protein content in the cerebral cortex and hippocampus of each group.It was found that,After intervention 30 days,compared with blank group,The learning and memory ability of rats in AD model group decreased significantly (P<0.01),The mRNA content and protein expression of Nrf2,NQO1,HO-1 in hippocampus and cerebral cortex of rats decreased significantly (P<0.01),while Keap1 mRNA content and protein expression increased significantly (P<0.01).Compared with the AD model group,the learning and memory abilities of rats in the donepezil hydrochloride and high,medium-dose groups of FOPS were significantly increased (P<0.01).The mRNA content and protein expression of Nrf2,NQO1,HO-1 in the hippocampus and cerebral cortex of rats was significantly increased (P<0.05,P<0.01),Keap1 mRNA content and protein expression were significantly reduced (P<0.05,P<0.01).In conclusion FOPS promoting the nuclear translocation of Nrf2 by regulating the expression of Keap1,inducing the expression of NQO1 and HO-1,and play a role in improving the bodys antioxidant damage,thereby improving the learning and memory ability of AD rats.

Key words: Fomes officinalis Ames polysaccharides, oxidative stress, Nrf2/ARE, cerebral cortex, hippocampus

中图分类号:  R932