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|本期目录/Table of Contents|

槲皮苷通过调节ROS和ATP保护缺氧原代皮层神经元的研究*(PDF)

《云南中医学院学报》[ISSN:1000-2723/CN:53-1048/R]

期数:
2018年04期
页码:
1-6
栏目:
实验研究
出版日期:
2019-03-25

文章信息/Info

Title:
Quercitin Protects Cerebral Cortical Neurons by Modulating ROS and ATP in Mitochondria
文章编号:
1000 - 2723(2018)04 - 0001 - 06
作者:
薛冰洁1黄吉生2马博1陈进成1刘建勋1△
(1. 中国中医科学院西苑医院基础医学研究所,北京 100091;2. 神威药业集团神威药物研究院,河北 三河 065201)
Author(s):
XUE Bingjie1 HUANG Jisheng2 MA Bo1 CHEN Jincheng1 LIU Jianxun1
(1. Institute of Basic Medical Science, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China; 2. Research Institute of Shineway Pharmaceutical Group, Sanhe 065201, China)
关键词:
槲皮苷 氧糖剥夺模型 细胞活力 ROS ATP
Keywords:
quercitin oxygen and glucose deprivation mitochondrial potential ROS ATP
分类号:
R285.5
DOI:
10.19288/j.cnki.issn.1000-2723.2018.04.001
文献标识码:
A
摘要:
目的对槲皮素干预ROS和ATP的产生改善缺氧原代皮层神经元进行研究。方法将怀孕18d左右的大鼠处死后取出胎鼠,提取大脑皮层神经元,采用氧糖剥夺模型,分为空白对照组、模型组、槲皮苷25 μM、12.5 μM以及6.25 μM组,每组6孔。除空白对照组外,其余各组均进行氧糖剥夺处理。氧糖剥夺3 h后,评价槲皮苷对缺氧神经元的细胞活力及细胞毒性的影响,并在此基础上探讨槲皮苷对ROS及ATP生成的调控作用。结果与空白对照组相比,模型组缺氧3 h后细胞活力显著下降(P<0.001),槲皮苷25、12.5、6.25 μM 3个剂量组均可以改善缺氧神经元的细胞形态,提高神经元活力,其中25 μM剂量组与模型组相比有显著性差异(P<0.01);此外,槲皮苷25、12.5、6.25 μM剂量均可以显著降低由缺氧引起的细胞毒性,与细胞活力类似,25 μM剂量组与模型组相比有显著性差异(P<0.05)。模型组的ROS在缺氧后与空白对照组相比明显升高(P<0.001),而槲皮苷25 μM、12.5 μM以及6.25 μM剂量组均可以显著降低缺氧神经元内ROS的含量(25 μM及12.5 μM(P<0.001);6.25 μM(P<0.05))。缺氧处理后,神经元内的ATP生成显著下降,与正常组相比差异显著(P<0.001);而与模型组相比,槲皮苷25 μM及12.5 μM剂量组均可以显著增加神经元内ATP的生成(25 μM及12.5 μM(P<0.001)。结论槲皮苷能够明显提高缺氧神经元的细胞活力,降低OGD引起的细胞毒性,其原因可能是由于槲皮苷通过调节ROS和ATP的生成,保护缺氧神经元免于死亡。
Abstract:
Objective To evaluate the protective effects a potential mechanisms of quercitin. Methods Following isolating neurons from E18 rat fetuses, we used an in vitro model of ischemic injury via oxygen and glucose deprivation(OGD) of cultured neurons. The OGD protocol was commenced by changing the culture medium to low-glucose HBSS and hypoxia condition at 37 ℃ for 3 h. For control cells that did not undergo OGD, the culture medium was replaced with regular glucose-containing culture medium and the neurons were grown under normal oxygen conditions. Following the OGD of cortical neurons, we measured cell viability(CCK-8) and cytotoxicity(LDH), and explored the potential mechanisms underlying the action of quercitin by integrating ROS and ATP. Results The 3-h OGD induced a significant decrease in cell viability and quercitin treatment induced a dose-dependent improvement in cell viability(P<0.01 at quercitin 25 μM) and decreased neuronal injuries characterized by the breakage of neuronal fibers and shrunken somas; the LDH assay indicated that there was a significant decrease in cytotoxicity following quercitin treatment(P<0.05 at quercitin 25 μM). ROS levels were greatly increased in neurons subjected to OGD; however, this OGD-induced excessive ROS production was significantly reversed by quercitin(P<0.001 at 25 and 12.5 μM and P<0.05 at 6.25 μM). ATP production was markedly declined following the 3-h OGD, but quercitin significantly increased ATP levels, seemingly in a dose-dependent manner (at 25 and 12.5 μM). Conclusion We revealed that quercitin treatment led to the decrease of ROS and improvement of ATP, which triggered the protection of mitochondria from quercitin, thereby protecting them from OGD-induced neuronal injury and death.

参考文献/References


[1] MIJAJLOVI M D, PAVLOVI A, BRAININ M, et al. Post-stroke dementia-a comprehensive review[J]. BMC Med,2017,15(1):11.
[2] KENNETH MAISES. The bright side of reactive oxygen species:lifespan extension without cellular demise[J]. J Transl Sci,2016,2:185-187.
[3] OUYANG Y B, STARY C M, WHITE R E, et al. The use of microRNAs to modulate redox and immune response to stroke[J]. Antioxid Redox Signal,2015,22(2):187-202.
[4] MATSUDA S, UMEDA M, UCHIDA H, et al. Alterations of oxidative stress markers and apoptosis markers in the striatum after transient focal cerebral ischemia in rats[J]. J Neural Transm,2009,116(4):395-404.
[5] HERRANZ-L?魷PEZ M, BORR?譧S-LINARES I, OLIVARES-VICENTE M, et al. Correlation between the cellular metabolism of quercetin and its glucuronide metabolite and oxidative stress in hypertrophied 3T3-L1 adipocytes[J]. Phytomedicine,2016,25:25-28.
[6] JOVEN J, ESPINEL E, RULL A, et al. Plant-derived polyphenols regulate expression of miRNA paralogs miR-103/107 and miR-122 and prevent diet-induced fatty liver disease in hyperlipidemic mice[J]. Biochim Biophys Acta,2012,1820(7):894-899.
[7] KAWAI Y, NISHIKAWA T, SHIBA Y, et al. Macrophage as a target of quercetin glucuronides in human atherosclerotic arteries:implication in the anti-atherosclerotic mechanism of dietary flavonoids[J]. J Biol Chem,2008,283(14):9424-9434.
[8] ISHISAKA A, MUKAI R, TERAO J, et al. Specific localization of quercetin-3-O-glucuronide in human brain[J]. Arch Biochem Biophys,2014,557:11-17.
[9] ZERNA C, HEGEDUS J, HILL M D. Evolving Treatments for Acute Ischemic Stroke[J]. Circ Res,2016,118(9):1425-1442.
[10] KAHL A, STEPANOVA A, KONRAD C, et al. Critical Role of Flavin and Glutathione in Complex I-Mediated Bioenergetic Failure in Brain Ischemia/Reperfusion Injury[J]. Stroke,2018,49(5):1223-1231.
[11] AGGARWAL A, AGGARWAL P, KHATAK M, et al. Cerebral ischemic stroke: Sequels of cascade[J]. International Journal of Pharma and Bio Sciences,2010,1(3):1.
[12] NOVGORODOV S A, RILEY C L, KEFFLER J A, et al. SIRT3 Deacetylates Ceramide Synthases:Implications for Mitochondrial Dysfunction and Brain Injury[J]. Journal of Biological Chemistry,2015,291(4):1957-1973.
[13] LIU Q, LI X, LI L, et al. Ginkgolide K protects SHSY5Y cells against oxygenglucose deprivationinduced injury by inhibiting the p38 and JNK signaling pathways[J]. Molecular Medicine Reports,2018,18(3):3185-3192.
[14] CADENAS E, DAVIES K J. Mitochondrial free radical generation,oxidative stress,and aging[J]. Free Radic Biol Med,2000,29(3):222-230.
[15] VALKO M, LEIBFRITZ D, MONCOL J, et al. Free radicals and antioxidants in normal physiological functions and human disease[J]. International Journal of Biochemistry & Cell Biology,2007,39(1):44-84.
[16] DUGAN L L, BEHRENS M M, ALI S S. Oxidative Stress in Hypoxic-Ischemic Brain Injury[M]. Brain Hypoxia and Ischemia. Totowa,New Jersey:Humana Press,2009:239-254.
[17] KALOGERIS T, BAINES C P, KRENZ M, et al. Ischemia/Reperfusion[J]. Compr Physiol,2016,7(1):113-170.
[18] ZHOU X, QI Y, CHEN T. Long-term pre-treatment of antioxidant Ginkgo biloba extract EGb-761 attenuates cerebral-ischemia-induced neuronal damage in aged mice[J]. Biomed Pharmacother,2017,85:256-263.
[19] RYU H, LEE J, IMPEY S, et al. Antioxidants modulate mitochondrial PKA and increase CREB binding to D-loop DNA of the mitochondrial genome in neurons[J]. Proc Natl Acad Sci USA. 2005,102(39):13915-13920.
[20] IOKU K, PONGPIRIYADACHA Y, KONISHI Y, et al. β-Gcosidase activity in the rat small intestine toward quercetin monoglucosides[J]. Biosci Biotechnol Biochem,1998,62(7):1428-1431.
[21] WALGREN R A, WALLE U K, WALLE T. Transport of Quercetin and Its Glucosides across Human Intestinal Epithelial Caco-2 Cells[J]. Biochemical Pharmacology,1998,55(10):1721-1727.
[22] HAM Y M, YOON W J, PARK S Y, et al. Quercitrin protects against oxidative stress-induced injury in lung fibroblast cells via up-regulation of Bcl-xL[J]. Journal of Functional Foods,2012,4(1):253-262.
[23] CHOI E M. Protective effect of quercitrin against hydrogen peroxide-induced dysfunction in osteoblastic MC3T3-E1 cells[J]. Experimental & Toxicologic Pathology,2012,64(3):211-216.
[24] CHOI J S, BAE J Y , KIM D S, et al. Dietary compound quercitrin dampens VEGF induction and PPARγ activation in oxidized LDL-exposed murine macrophages: Association with scavenger receptor CD36[J]. Journal of Agricultural & Food Chemistry,2010,58(2):1333-41.
[25] WAGNER C, FACHINETTO R, DALLA CORTE C L,et al. Quercitrin,a glycoside form of quercetin,prevents lipid peroxidation in vitro[J]. Brain research,2006,1107(1):192-198.
[26] F S?NCHEZ DE MEDINA, VERA B, J G?LVEZ, et al. Effect of quercitrin on the early stages of hapten induced colonic inflammation in the rat[J]. Life Sciences,2002,70(26):3097-3108.
[27] CAMUESCO D, COMALADA M, RODR?魱GUEZ-CABEZAS M E, et al. The intestinal anti-inflammatory effect of quercitrin is associated with an inhibition in iNOS expression[J]. British journal of pharmacology,2004,143(7):908-918.
[28] MA J Q, LUO R Z, JIANG H X, et al. Quercitrin offers protection against brain injury in mice by inhibiting oxidative stress and inflammation[J]. Food Funct,2016,7(1):549-556.

备注/Memo

备注/Memo:
收稿日期: 2018 - 06- 12 *
*基金项目: 国家自然科学基金青年基金项目(81703747);国家重点基础研究发展计划(973)项目(2015CB554405);中国 博士后基金项目(2017M621041)
第一作者简介: 薛冰洁(1984-),女,博士,助理研究员,研究方向:脑神经及中风。
△通信作者: 刘建勋,E-mail:liujx0325@sina.com
更新日期/Last Update: 2018-10-30