一氧化氮和天然抗氧化剂对阿尔茨海默症的潜在防治作用
Preventive and Therapeutic Effects of Nitric Oxide and Natural Antioxidants on Alzheimer’s Disease

作者: 陈梦媛 , 李 超 , 赵 燕 :哈尔滨工业大学(威海)生物工程系,山东 威海; 张 娟 , 刘 强 :中国科学技术大学生命科学学院,中科院脑功能与脑疾病重点实验室,安徽 合肥; 张智贤 , 徐 力 :吉林大学生命科学学院,吉林 长春 ;

关键词: 一氧化氮天然抗氧化剂阿尔茨海默症活性氧Nitric Oxide Natural Antioxidants Alzheimer’s Disease Reactive Oxygen Species

摘要:
本文以转基因细胞和线虫体系为模型,研究了一氧化氮(nitric oxide, NO)和天然抗氧化剂的合理搭配组合对阿尔茨海默症(Alzheimer’s disease, AD)的防治作用。结果发现,低浓度的NO可以通过降低细胞内活性氧的水平保护神经细胞,防止APPsw和ApoE4过量表达引起的损伤作用;而高浓度的NO可以通过增强活性氧(reactive oxygen species, ROS)的产生加剧神经细胞损伤。适量NO和天然抗氧化剂都对Abeta转基因诱导的线虫瘫痪行为具有抑制作用。NO和天然抗氧化剂的合理搭配组合既可以通过显著清除ROS抑制ApoE4和APPsw转基因引起的细胞活力降低,又可以更好的延缓Abeta转基因诱导的线虫瘫痪行为。这些结果说明,NO和天然抗氧化剂合理搭配可以在AD细胞和线虫模型中抑制转基因引起的细胞和线虫的损伤,有可能对AD具有一定的防治作用。

Abstract: In this study, the preventive and therapeutic potential of nitric oxide (NO) and natural antioxidants on Alzheimer’s disease (AD) were studied using transgenic cells and C. elegans models. It was found that low concentration of NO protected neuronal cells by reducing the production of reactive oxygen species (ROS). In contrast, high concentration of NO aggravated the cell damage by producing more ROS. Low concentration of NO and natural antioxidant could protect C. elegans against paralysis induced by expression of transgenic Abeta gene. It was found that a formulation of L-arginine and natural antioxidants increased the viability of N2a cells overexpressing APPsw and ApoE4 by scavenging ROS. This formula also protected C. elegans against paralysis caused by transgenic Abeta gene. These results suggest that this formulation of NO precursor and natural antioxidants may have a potential for prevention and treatment of AD.

文章引用: 陈梦媛 , 张 娟 , 李 超 , 张智贤 , 徐 力 , 刘 强 , 赵 燕 (2016) 一氧化氮和天然抗氧化剂对阿尔茨海默症的潜在防治作用。 食品与营养科学, 5, 105-113. doi: 10.12677/HJFNS.2016.53014

参考文献

[1] Querfurth, H.W. and La Ferla, F.M. (2010) Alzheimer’s Disease. The New England Journal of Medicine, 362, 329- 344.
http://dx.doi.org/10.1056/NEJMra0909142

[2] Ferri, C.P., Prince, M., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., Hall, K., Hasegawa, K., Hendrie, H., Huang, Y., Jorm, A., Mathers, C., Menezes, P.R., Rimmer, E., Scazufca, M., Alzheimer’s Dis-ease International (2005) Global Prevalence of Dementia: A Delphi Consensus Study. The Lancet, 366, 2112-2117.
http://dx.doi.org/10.1016/S0140-6736(05)67889-0

[3] Dong, M.J., Peng, B., Lin, X.T., Zhao, J., Zhou, Y.R. and Wang, R.H. (2007) The Prevalence of Dementia in the People’s Republic of China: A Systematic Analysis of 1980-2004 Studies. Age Ageing, 36, 619-624.
http://dx.doi.org/10.1093/ageing/afm128

[4] Guix, F.X., Uribesalgo, I., Coma, M. and Muñoz, F.J. (2005) The Physiology and Pathophysiology of Nitric Oxide in the Brain. Progress in Neurobiology, 76, 126-152.
http://dx.doi.org/10.1016/j.pneurobio.2005.06.001

[5] Fernandez-Tome, P., Lizasoain, I., Leza, J.C., Lorenzo, P. and Moro, M.A. (1999) Neuroprotective Effects of, a Nitric Oxide Donor, on Hydrogen Peroxide-Induced Neurotoxicity in Cortical Neurones. Neuropharmacology, 38, 1307- 1315.
http://dx.doi.org/10.1016/S0028-3908(99)00069-6

[6] Ciani, E., Guidi, S., Della Valle, G., Perini, G., Bartesaghi, R. and Contestabile, A. (2002) Nitric Oxide Protects Neuroblastoma Cells from Apoptosis Induced by Serum Deprivation through cAMP-Response Element-Binding Protein (CREB) Activation. The Journal of Biological Chemistry, 277, 49896-49902.
http://dx.doi.org/10.1074/jbc.M206177200

[7] Fatokun, A.A., Stone, T.W. and Smith, R.A. (2008) Prolonged Exposures of Cerebellar Granule Neurons to S-Nitroso- N-Acetylpenicillamine (SNAP) Induce Neuronal Damage Independently of Peroxynitrite. Brain Research, 1230, 265- 272.
http://dx.doi.org/10.1016/j.brainres.2008.06.109

[8] Shen, J., Wang, J., Zhao, B., Hou, J., Gao, T. and Xin, W. (1998) Effects of EGb-761 on Nitric Oxide, Oxygen Free Radicals, Myocardial Damage and Arrhythmias in Ischemia-Reperfusion Injury in Vivo. Biochimica et Biophysica Acta, 1406, 228-236.
http://dx.doi.org/10.1016/S0925-4439(98)00007-6

[9] Shen, J., Li, M., Xin, W. and Zhao, B. (2000) Effects of Chinonin on Nitric Oxide Free Radical, Myocardial Damage and Arrhythmia in Ischemia-Reperfusion Injury in Vivo. Applied Magnetic Resonance, 19, 9-19.
http://dx.doi.org/10.1007/BF03162257

[10] Zhang, D. and Zhao, B. (2004) Oral Administration of Crataegus Extraction Protects against Ischemia/Reperfusion Brain Damage in the Mongolian Gerbils. Journal of Neurochemistry, 90, 211-219.
http://dx.doi.org/10.1111/j.1471-4159.2004.02480.x

[11] Zhao, B. (2015) “Double Edge” Effects of Nitric Oxide Free Radical in Cardio-Brain-Vascular Diseases and Health Studied by ESR. Chinese Journal of Magnetic Resonance, 32, 195-207.

[12] Palmer, R.M., Ferrige, A.G. and Moncada, S. (1987) Nitric Oxide Release Accounts for the Biological Activity of Endothelium-Derived Relaxing Factor. Nature, 327, 524-526.
http://dx.doi.org/10.1038/327524a0

[13] Furchgott, R.F. and Vanhoutte, P.M. (1989) Endothelium-Derived Relaxing and Contracting Factors. The FASEB Journal, 3, 2007-2018.

[14] Contestabile, A. and Ciani, E. (2004) Role of Nitric Oxide in the Regulation of Neuronal Proliferation, Survival and Differentiation. Neurochemistry International, 45, 903-914.
http://dx.doi.org/10.1016/j.neuint.2004.03.021

[15] Calabrese, V., Mancuso, C., Calvani, M., Rizzarelli, E., Butterfield, D.A. and Stella, A.M. (2007) Nitric Oxide in the Central Nervous System: Neuroprotection versus Neurotoxicity. Nature Reviews Neuroscience, 8, 766-775.
http://dx.doi.org/10.1038/nrn2214

[16] Higuera-Ciapara, I., Felix-Valenzuela, L. and Goycoolea, F. (2006) Astaxanthin: A Review of Its Chemistry and Applications. Critical Reviews in Food Science and Nutrition, 46, 185-196.
http://dx.doi.org/10.1080/10408690590957188

[17] Ikeda, Y., Tsuji, S., Satoh, A., Ishikura, M., Shirasawa, T. and Shimizu, T. (2008) Protective Effects of Astaxanthin on 6-Hydroxydopamine-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells. Journal of Neurochemistry, 107, 1730-1740.
http://dx.doi.org/10.1111/j.1471-4159.2008.05743.x

[18] Chang, C., Chen, C., Chiou, J., Peng, R. and Peng, C. (2010) Astaxanthine Secured Apoptotic Death of PC12 Cells Induced by Beta-Amyloid Peptide 25-35: Its Molecular Action Targets. Journal of Medicinal Food, 13, 548-556.
http://dx.doi.org/10.1089/jmf.2009.1291

[19] Shen, H., Kuo, C., Chou, J., Delvolve, A., Jackson, S.N., Post, J., Woods, A.S., Hoffer, B.J., Wang, Y. and Harvey, B.K. (2009) Astaxanthin Reduces Ischemic Brain Injury in Adult Rats. The FASEB Journal, 23, 1958-1968.
http://dx.doi.org/10.1096/fj.08-123281

[20] Al Makdessi, S., Sweidan, H., Dietz, K. and Jacob, R. (1999) Protective Effect of Crataegus Oxyacantha against Reperfusion Arrhythmias after Global No-Flow Ischemia in the Rat Heart. Basic Research in Cardiology, 94, 71-77.
http://dx.doi.org/10.1007/s003950050128

[21] Petkov, E., Nikolov, N. and Uzunov, P. (1981) Inhibitory Effect of Some Fla-vonoids and Falvonoid Mixtures on Cyclic Amp Phosphodiesterase Activity of Rat Heart. Planta Medica, 43,183-186.
http://dx.doi.org/10.1055/s-2007-971497

[22] Li, L.D., Li, Y.G., Gao, F.H., Liu, Z., Zhang, J. and Yu, L. (1984) Studies on Hawthorn and Its Active Principle. II. Effects on Cultured Rat Heart Cells Deprived of Oxygen and Glucose. Journal of Traditional Chinese Medicine, 4, 289-292.

[23] Walker, A.F., Marakis, G., Morris, A.P. and Robinson, P.A. (2002) Promising Hypotensive Effect of Hawthorn Extract: A Randomized Double-Blind Pilot Study of Mild, Essential Hypertension. Phytotherapy Research, 16, 48-54.
http://dx.doi.org/10.1002/ptr.947

[24] Zhao, B., Shen, J., Li, M., Li, M., Wan, Q. and Xin, W. (1996) Scavenging Effect of Chinonin on NO and Oxygen Free Radicals and Its Protective Effect on the Myocardium from the Injury of Ischemia-Reperfusion. Biochimica et Biophysica Acta, 1315, 131-137.
http://dx.doi.org/10.1016/0925-4439(95)00112-3

[25] Shen, J.G., Guo, X.S., Jiang, B., Li, M., Xin, W. and Zhao, B. (2000) Chinonin, a Novel Drug against Cardiomyocyte Apoptosis Induced by Hypoxia and Reoxygenation. Biochimica et Biophysica Acta, 1500, 217-226.
http://dx.doi.org/10.1016/S0925-4439(99)00109-X

[26] Coleman, J.W. (2001) Nitric Oxide in Immunity and Inflammation. International Immunopharmacology, 1, 1397- 1406.
http://dx.doi.org/10.1016/S1567-5769(01)00086-8

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