天然产物研究与开发 ›› 2021, Vol. 33 ›› Issue (1): 73-78.doi: 10.16333/j.1001-6880.2021.1.010

• 开发研究 • 上一篇    下一篇

异槲皮苷对Aβ25-35导致的PC12细胞损伤的保护作用及机制研究

郑传痴1，周旭美2，高健美2*   

  1. 1遵义医科大学第二附属医院药剂科；2遵义医科大学药学院，遵义 563000

  • 出版日期:2021-01-28 发布日期:2021-01-28
  • 基金资助:
    贵州省科技厅与遵义医科大学附属医院联合基金（黔科合LH字［2015］7484号）

Protective effect and mechanism of isoquercitrin on Aβ25-35-induced PC12 cell injury

ZHENG Chuan-chi1,ZHOU Xu-mei2,GAO Jian-mei2*   

  1. 1Pharmacy Department,the Second Affilicated Hospital of Zunyi Medical University;2School of Pharmacy,Zunyi Medical University,Zunyi 563000,China

  • Online:2021-01-28 Published:2021-01-28

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摘要：

探讨异槲皮苷对β-淀粉样蛋白（ Aβ25-35）导致的PC12细胞氧化损伤的保护作用。首先通过分子对接技术分析异槲皮苷与AMPK的结合情况。采用A Aβ25-35（20 μmol/L）损伤PC12细胞建立细胞氧化损伤模型，采用甲基噻唑蓝（MTT）法检测细胞活力，通过试剂盒检测乳酸脱氢酶（LDH）漏出量、活性氧（ROS）含量、丙二醛（MDA）含量以及抗氧化物酶超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活力，采用Western blot法检测磷酸化腺苷酸活化蛋白激酶（p-AMPK）、过氧化物增殖体受体辅激活子-1α（PGC-1α）、沉默信息调节因子3（Sirt3）和异柠檬酸脱氢酶（IDH2）的蛋白表达。结果显示异槲皮苷与AMPK的结合力为-9.48 kJ/mol，提示AMPK可能为异槲皮苷的潜在作用靶点。异槲皮苷（1、10和100 μmol/L）能够浓度依赖性的显著抑制Aβ25-35导致的PC12细胞死亡，减少ROS和MDA含量，升高SOD和GSH-Px活力。异槲皮苷抑制 Aβ25-35导致的细胞氧化损伤并上调p-AMPK、PGC-1α、Sirt3和IDH2的蛋白表达。以上结果表明异槲皮苷可能通过调控AMPK/Sirt3信号通路发挥抗Aβ25-35导致的PC12细胞氧化损伤作用。

关键词: 异槲皮苷, β-淀粉样蛋白25-35, PC12细胞, 氧化应激, 沉默信息调节因子3

Abstract:

To explore protective effect of isoquercitrin on Aβ25-35-induced injury in PC12 cells.The interaction of isoquercitrin with AMPK was determined by molecular docking.Aβ25-35 (20 μmol/L) -induced PC12 cells injury was accepted as an model of oxidative stress in vitro.Cell viability was detected using MTT assay,LDH release,ROS content,MDA content and antioxidant enzymes including SOD and GSH-Px activities were measured by corresponding kits.Expressions of p-AMPK,PGC-1α,Sirt3 and IDH2 proteins were determined using Western blot analysis.The results showed that the binding energy between isoquercitrin and AMPK was -9.48 kJ/mol.Pre-treatment with isoquercitrin (1,10,100 μmol/L) concentration-dependent suppressed PC12 cell death-induced by Aβ25-35.Isoquercitrin not only decreased ROS and MDA contents,but also elevated SOD and GSH-Px activities. Furthermore,isoquercitrin also up-regulated p-AMPK,PGC-1α,Sirt3 and IDH2 protein expressions.These findings indicated that isoquercitrin protected against Aβ25-35-induced oxidative injury in PC12 via AMPK/Sirt3 signaling pathway.

Key words: isoquercitrin, Aβ25-35, PC12 cells, oxidative stress, sirtuin 3 ,

中图分类号:  R285.5

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