[1]王 钧,张浩萌 ,张文彤 ,等.新型双香豆素类化合物通过Nrf 2/ARE通路诱导OGD神经元保护研究*[J].陕西医学杂志,2019,(6):683-687.
　WANG Jun,ZHANG Haomeng,ZHANG Wentong,et al.A new biscoumarin compound protects against neuronal oxygen and glucose deprivation via Nrf 2/ARE pathway[J].,2019,(6):683-687.
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新型双香豆素类化合物通过Nrf 2/ARE通路诱导OGD神经元保护研究*
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2019年6期
页码:
683-687
栏目:
基础研究
出版日期:
2019-06-05

文章信息/Info

Title:
A new biscoumarin compound protects against neuronal oxygen and glucose deprivation via Nrf 2/ARE pathway
文章编号:
DOI:〖HT5K〗10.3969/j.issn.1000-7377.2019.06.001
作者:
王 钧1 ; 张浩萌2 ; 张文彤1 ; 樊朝阳3 ; 李 侠1
1.空军军医大学第一附属医院(西安 710032)；2.空军军医大学第二附属医院(西安 710038)；3.空军军医大学药理系（西安710032）
Author(s):
WANG Jun;  ZHANG Haomeng; ZHANG Wentong; et al.
First Affiliated Hospital of Air Force Medical University (Xi＇an 710032)
关键词:
氧糖剥夺模型; 神经元; 氧化应激; Nrf 2/ARE信号通路
Keywords:
Key words Oxygen and glucose deprivation; Neuron; Oxidative stress; Nrf 2/ARE pathway
分类号:
R392.5
文献标志码:
A
摘要:
摘 要 〖HT5K〗目的：探讨新型双香豆素类化合物3-CF3-4-CL对氧糖剥夺损伤（OGD）神经元诱发氧化应激的影响和潜在作用机制。方法：原代培养小鼠皮层神经元，建立OGD模型模拟脑缺血再灌注损伤；以Cell Counting Kit-8(CCK-8)法检测3-CF3-4-CL对细胞生存率的影响；q-PCR检测四种抗氧化因子的mRNA表达；以丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶(GSH-Px)为细胞氧化水平指标；Western blot检测Nrf 2/ARE信号通路蛋白水平变化。结果：与对照组相比，3-CF3-4-CL处理组细胞生存率提高，抗氧化因子mRNA表达量升高，SOD和GSH-Px表达水平升高，MDA含量降低；3-CF3-4-CL处理组细胞核因子E2相关因子2（Nrf 2）总蛋白活化水平升高，细胞核Nrf 2蛋白水平表达升高；同时，其下游抗氧化蛋白血红素氧合酶-1（HO-1）表达水平升高。结论：新型双香豆素类化合物3-CF3-4-CL通过激活Nrf 2/ARE信号通路，提高OGD损伤神经元的抗氧化应激水平，发挥神经保护功能。
Abstract:
Abstract Objective: To investigate the effect and potential mechanism of a new type biscoumarin compound named 3-CF3-4-CL, during protection against oxidative stress caused by Oxygen and glucose deprivation (OGD) in neurons. Methods: The in vitro model to assess the mechanism of oxidative stress in I/R was established by OGD of neurons. The cell viability was measured by CCK-8 assay. The mRNA levels of four antioxidant elements was measured by q-PCR. Oxidative stress indicators was detected by malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px). The effects of 3-CF3-4-CL on nuclear translocation of Nrf 2 and protein expression of hemeoxygenase-1 (HO-1) were measured by western blot. Results: Compared with the control group，in 3-CF3-4-CL treated group the cell viability of neurons increased obviously, the mRNA of four antioxidant elements increased, 3-CF3-4-CL improved SOD and GSH-Px activation, reduced MDA content. Moreover, 3-CF3-4-CL could induce activation and nuclear translocation of nuclear factor E2 related factor 2 (Nrf 2) and significantly increased protein expression of HO-1 when compared with OGD group. Conclusion: 3-CF3-4-CL may protect against damage of oxidative stress in OGD model of neurons via activation of Nrf 2/ARE pathway.

参考文献/References:

[1] Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke [J]. Int J Stroke, 2009, 4(6): 461-470.
[2] 董 妍, 曾维惠, 李文彬. 姜黄素对H2O2诱导人黑素细胞氧化应激损伤的预保护作用[J]. 陕西医学杂志, 2017,46(2):220-223.
[3] 王 军, 曹 艳, 王警卫,等. 异丙酚对大鼠局灶性脑缺血再灌注损伤的保护作用[J]. 陕西医学杂志, 2014,43(6):660-661.
[4] Psrfenov A, Smirnov LD. Pharmacological potential of antioxidants derived from coumarin (Review) [J]. Pharm Chem J, 1988, 22(12): 884-892.
[5] Al-amiery AA, Al-Bayatir IH, Saour KY, et al. Cytotoxicity, antioxidant, and antimicrobial activities of novel 2-quinolone derivatives derived from coumarin [J]. Res Chem Intermediat, 2012, 38(2): 559-569.
[6] 王 军, 曹 艳, 常江, 等. n-3多不饱和脂肪酸对大鼠脑缺血再灌注影响及其机制[J]. 陕西医学杂志, 2015(10):1290-1292..
[7] Ishihara Y， Katayama K， Sakabe M， et al． Antioxidant properties of rare sugar D-allose: Effects on mitochondrial reactive oxygen species production in Neuro2A cells ［J］. J Biosci Bioeng, 2011, 112(6):638-642.
[8] 邢 东, 董 辉, 朱明霞. 体外培养大鼠皮层神经元和星形胶质细胞氧糖剥夺后DDR1的表达情况[J]. 陕西医学杂志, 2014,41(2):167-169.
[9] Vendatasairam K, Gurupadayya BM, Chandan RS, et al. A review on chemical profile of coumarins and their therapeutic role in the treatment of cancer [J]. Curr Drug Deliv, 2016, 13(2): 186-201.
[10] 宋江莉, 袁 婕. 钙拮抗剂对大鼠脑缺血后血脑屏障通透性的影响[J]. 陕西医学杂志, 2017,46(1):7-8,23.
[11] Kim SS, Lim J, Bang Y, et al. Licochalcone E activates Nrf 2/antioxidant response element signaling pathway in both neuronal and microglial cells: therapeutic relevance to neurodegenerative disease [J]. J Nutr Biochem, 2012, 23(10): 1314-1323.
[12] Guichard C, Pedruzzi E, Fay M, et al. The Nox/Duox family of ROS-generating NADPH oxidases [J]. Med Sci, 2006, 22(11): 953-959.
[13] 王 涛, 贺中正, 朱 莽, 等. 依达拉奉对重型颅脑损伤患者急性期脑水肿及神经功能的影响[J]. 陕西医学杂志, 2017,46(1):34-36.
[14] Son TG, Ccmandola S, Arumugam TV, et al. Plumbagin, a novel Nrf 2/ARE activator, protects against cerebral Ischemia [J]. J Neuro Chem, 2010, 112(5): 1316-1326.

备注/Memo

备注/Memo:
*陕西省科技统筹创新工程计划项目(2014KTCL03-03)
更新日期/Last Update: 2019-06-20