[1]王莹莹,宋修云,王 奇,等.人参皂苷Rg1通过抗氧化应激保护冈田酸诱导的PC12细胞损伤[J].中国药理学通报,2016,(10):1364-1370.[doi:10.3969/j.issn.1001-1978.2016.10.008]
 WANG Ying-ying,SONG Xiu-yun,WANG Qi,et al.The protective effects of Ginsenosides Rg1 in AD-like pathological model induced by okadaic acid[J].Chinese Pharmacological Bulletin,2016,(10):1364-1370.[doi:10.3969/j.issn.1001-1978.2016.10.008]
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人参皂苷Rg1通过抗氧化应激保护冈田酸诱导的PC12细胞损伤()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2016年10期
页码:
1364-1370
栏目:
论著
出版日期:
2016-10-15

文章信息/Info

Title:
The protective effects of Ginsenosides Rg1 in AD-like pathological model induced by okadaic acid
文章编号:
1001-1978(2016)10-1364-07
作者:
王莹莹13宋修云1王 奇3陈乃宏1 2
1. 中国医学科学院,药物研究所&神经科学中心,北京 100050;
2. 湖南中医药大学药学院,湖南 长沙 410208 3. 广州中医药大学,临床药理研究所,广东 广州 510000
Author(s):
WANG Ying-ying13SONG Xiu-yun1WANG Qi3CHEN Nai-hong12
1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;
2. Hunan University of Chinese Medicine,Changsha 410208,China;
3. Guangzhou University of Chinese Medicine, Institute of Clinical Pharmacology,Guangzhou 510000,China
关键词:
人参皂苷Rg1 冈田酸 阿尔茨海默病 氧化应激 凋亡 神经保护
Keywords:
Ginsenosides Rg1 okadaic acid Alzheimer's disease oxidative stress apoptosis neuroprotection
分类号:
R284.1;R329.24;R329.25;R745.7;R977.3
DOI:
10.3969/j.issn.1001-1978.2016.10.008
文献标志码:
A
摘要:
目的 体外细胞水平研究人参皂苷Rg1在冈田酸(Okadaic Acid,OKA)诱导的阿尔茨海默病(Alzheimer's disease, AD)样神经毒性模型中的保护作用,并初步探索其作用机制。方法 选用PC12细胞模拟神经元,采用OKA造模的同时给予Rg1(1、5、10 μmol·L-1-),选用褪黑素(Melatonin, Melat)10 μmol·L-1-作为阳性对照。分别采用MTT、LDH法检测细胞存活率及死亡率,采用流式细胞术检测细胞凋亡情况,用DCFH-DA荧光探针法检测胞内ROS的堆积,并用试剂盒检测细胞内一系列抗氧化酶活性的变化。结果 与对照组相比,OKA组细胞存活率明显降低、死亡率明显增加,细胞早期凋亡数量明显增多(P<0.01); 氧化应激相关指标检测发现,OKA组胞内ROS堆积明显增多(P<0.01),总抗氧化能力(ABTS)明显降低(P<0.01),过氧化物酶(Catalase, CAT)(P<0.01),超氧化物歧化酶(Superoxide Dismutase, SOD)、谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)活性都明显降低(P<0.05),GSSG/GSH比率明显升高(P<0.01)。与模型组相比,Rg1不同剂量组均能显著提高OKA模型中PC12细胞的存活率,降低细胞死亡率,并抑制胞内ROS水平、提高抗氧化酶活力增强抗氧化能力。结论 人参皂苷Rg1在OKA诱导的AD样病理模型中可以通过抗氧化应激作用发挥抗细胞死亡、保护神经细胞的作用。
Abstract:
Aim To the investigate the protective effect of ginsenoside Rg1 in Alzheimer's disease(AD)-like neurotoxicity model induced by okadaic acid(OKA)in the cellular level, and explore the mecha-nism preliminarily. Methods The PC12 cells model, simulate neurons, induced by OKA was given Rg1(1,5,10 μmol·L-1), and melatonin(Melat)10 μmol·L-1 was given as a positive control. MTT and LDH were carried out to assess the cell viability and mortality. To detect the accumulation of ROS, the DCFH-DA fluorescent probe was conducted. And to assess the change of the activity of a variety of antioxidant enzymes, various kits were used, including ABTS、CAT、SOD、GSH-Px and GSSG/GSH. Results Compared with the control group, the survival rate of PC12 cell in OKA group reduces significantly, the mortality rate was increased significantly, the number of early apoptotic cells was increased significantly(P<0.01). Oxidative stress-related indicators show that ROS accumulation within the cells of OKA group increases significantly(P<0.01), and the total antioxidant capacity(ABTS)decreases significantly(P<0.01), the activity of peroxidase(Catalase, CAT)(P<0.01), glutathione peroxidase(glutathione peroxidase, GSH-Px)and superoxide dismutase(superoxide dismutase, SOD)decreased significantly(P<0.05), the rate of GSSG/GSH increased significantly(P<0.01). Compared with the model group, the different doses of Rg1 could improve the survival rate and decrease the mortality rate of PC12 cell significantly in the group of OKA, and could decrease the level of the accumulation of ROS, improve the activity of antioxidant enzymes. Conclusion Ginsenoside Rg1 can decrease PC12 cell apoptosis by exerting antioxidant effects, and protect the nerve cells in AD-like pathology model induced by OKA.

参考文献/References:

[1] 段 磊,司继刚,刘 萍. 阿尔茨海默病药物治疗研究进展[J]. 河北医药,2015,7:1077-80. [1] Duan L, Si J P, Liu P. Progress in Drug Therapy for Alzheimer's Disease [J]. Hebei Med J, 2015, 07: 1077-80.
[2] 周 玥,姜 蓉,姚 欣,等. 人参皂苷Rg_1在造血干/祖细胞连续移植中抗细胞衰老的作用机制[J]. 中草药,2013,44(21):3172-5.
[2] Zhou Y, Jiang R, Yao X, et al. Mechanism of ginsenoside Rg1 against hematopoietic stem/progenitor cells senescence during serial transplantation[J]. Chin Trad Herb Drugs,2013,44(21):3172-5.
[3] 李成鹏,张梦思,刘 俊,等. 人参皂苷Rg_1延缓脑衰老机制研究[J]. 中国中药杂志,2014,22:4442-7.
[3] Li C P, Zhang M C, Liu J, et al. Research of anti-aging mechanism of ginsenoside Rg1 on brain[J]. China J Chin Mater Med, 2014, 22: 4442-7.
[4] Song X Y, Hu J F, Chu S F, et al. Ginsenoside Rg1 attenuates okadaic acid induced spatial memory impairment by the GSK3β/tau signaling pathway and the Aβ formation prevention in rats[J]. Eur J Pharmacol, 2013,710(1-3):29-38.
[5] 李 娜. 人参皂苷Rg1治疗神经退行性疾病的研究进展[J]. 中国老年学杂志,2012,32(15):1-5.
[5] Li N.Research progress of ginsenoside Rg1 in the treatment of neurodegenerative diseases[J]. Chin J Gerontol,2012,32(15):1-5.
[6] Kamat P K, Rai S, Swarnkar S,et al. Molecular and cellular mechanism of okadaic acid(OKA)-induced neurotoxicity: a novel tool for Alzheimer's disease therapeutic application[J]. Mol Neurobiol, 2014,50(3):852-65.
[7] Kamat P K, Nath C. Okadaic acid: a tool to study regulatory mechanisms for neurodegeneration and regeneration in Alzheimer's disease[J]. Neural Regen Res, 2015,10(3):365-7.
[8] Pandi-Perumal S R,BaHammam A S,Brown G M,et al.Melatonin antioxidative defense:therapeutical implications for aging and neurodegenerative processes[J].Neurotox Res,2013,23(3):267-300.
[9] Deng Y, Jiao C, Mi C,et al. Melatonin inhibits manganese-induced motor dysfunction and neuronal loss in mice: involvement of oxidative stress and dopaminergic neurodegeneration[J]. Mol Neurobiol, 2015, 51(1):68-88.
[10] Navarro-Yepes J, Zavala-Flores L, Anandhan A,et al. Antioxidant gene therapy against neuronal cell death[J]. Pharmacol Ther, 2014,142(2):206-30.
[11] Lipton P. Ischemic cell death in brain neurons[J]. Physiol Rev, 1999, 79(4):1431-568.
[12] Shen L,Zhang J. NMDA receptor and iNOS are involved in the effects of Ginsenoside Rg1 on hippocampal neurogenesis in ischemic gerbils[J].Neurol Res,2007,29(3):270-3.
[13] 廖永晖,汤雨,千年松,等. 氧化应激与细胞凋亡[J]. 新乡医学院学报,2011,28(1):110-3.
[13] Liao Y H,Tang Y,Qian N S, et al. Oxidative stress and apoptosis[J]. J Xinxiang Med Coll, 2011,28(1):110-3.
[14] 黄天文,何饶丽,周 梦,等. 人参皂苷Rg1对寡聚肽Aβ_(1-42)增加JNK活性及诱导凋亡的影响[J]. 中国药理学通报,2015,31(1):60-3.
[14] Huang T W, He R L, Zhou M, et al. Effect of ginsenoside Rg1 on JNK and oligomeric Aβ1-42 induced apoptosis[J]. Chin Pharmacol Bull, 2015,31(1):60-3.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金项目(81274122、81373997、81273629、21272278、U1402221、81573640、81573636、81260650); 北京市自然科学基金项目(7131013、7142115); 湖南省重点研发计划项目(2015SK2029-1); 湖南省教育厅高校科研经费开放基金项目(15K091); 新药作用机制研究与药效评价北京市重点实验室资助项目(BZ0150)
作者简介:王莹莹(1992-),女,硕士生; E-mail:wangyingyingwangye@163.com;
陈乃宏(1961-),男,博士后,研究员,研究方向:神经药理学和神经分子生物学,通讯作者,Tel:010-63165177,E-mail:chennh@imm.ac.cn;
王 奇(1963-),男,研究员,研究方向:临床流行病学/DME应用研究以及中药临床试验、老年性痴呆临床与实验研究,E-mail:wqitcm@qq.com
更新日期/Last Update: 2016-10-15